Pathogenesis, Assessment, and Treatment of Coronary Microcirculation Dysfunction. / Patogênese, Avaliação e Tratamento da Disfunção da Microcirculação Coronariana.

Cardiovascular disease is the predominant cause of mortality on a global scale. Research indicates that women exhibit a greater likelihood of presenting with non-obstructive coronary artery disease (CAD) when experiencing symptoms of myocardial ischemia in comparison to men. Additionally, women tend to experience a higher burden of symptoms relative to men, and despite the presence of ischemic heart disease, they are frequently reassured erroneously due to the absence of obstructive CAD. In cases of ischemic heart disease accompanied by symptoms of myocardial ischemia but lacking obstructive CAD, it is imperative to consider coronary microvascular dysfunction as a potential underlying cause. Coronary microvascular dysfunction, characterized by impaired coronary flow reserve resulting from functional and/or structural abnormalities in the microcirculation, is linked to adverse cardiovascular outcomes. Lifestyle modifications and the use of anti-atherosclerotic and anti-anginal medications may offer potential benefits, although further clinical trials are necessary to inform treatment strategies. This review aims to explore the prevalence, underlying mechanisms, diagnostic approaches, and therapeutic interventions for coronary microvascular dysfunction.

A doença cardiovascular é a causa predominante de mortalidade em escala global. A pesquisa indica que as mulheres, em comparação aos homens, apresentam maior probabilidade de apresentar doença arterial coronariana (DAC) não obstrutiva quando têm sintomas de isquemia miocárdica. Além disso, as mulheres tendem a apresentar uma maior carga de sintomas em relação aos homens e, apesar da presença de doença cardíaca isquêmica, são frequentemente tranquilizadas erroneamente devido à ausência de DAC obstrutiva. Nos casos de cardiopatia isquêmica acompanhada de sintomas de isquemia miocárdica, mas sem DAC obstrutiva, é imperativo considerar a disfunção microvascular coronariana como uma potencial causa subjacente. A disfunção microvascular coronariana, caracterizada por reserva de fluxo coronariano prejudicada resultante de anormalidades funcionais e/ou estruturais na microcirculação, está associada a desfechos cardiovasculares adversos. Modificações no estilo de vida e o uso de medicamentos antiateroscleróticos e antianginosos podem oferecer benefícios potenciais, embora sejam necessários mais ensaios clínicos para informar estratégias de tratamento. Esta revisão tem como objetivo explorar a prevalência, mecanismos subjacentes, abordagens diagnósticas e intervenções terapêuticas para disfunção microvascular coronariana.

Safety and Efficacy of Adipose-Derived Mesenchymal Stem Cell Therapy for Ischemic Heart Disease: A Systematic Review. / Segurança e Eficácia da Terapia com Células-tronco Mesenquimais Derivadas do Tecido Adiposo para Cardiopatia Isquêmica: Revisão Sistemática.

BACKGROUND: Cell therapy using adipose-derived mesenchymal stem cells (ADSCs) shows great potential as a treatment for cardiovascular diseases. OBJECTIVE: We conducted a systematic review to describe the safety and efficacy of ADSCs in ischemic heart disease. METHODS: We searched PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL, and LILACS (from inception to March 2024) for clinical studies involving ADSCs in patients with ischemic heart disease. We excluded studies involving patients with other types of heart disease, studies using mesenchymal stem cells derived from other tissues, as well as ongoing studies. Two independent reviewers screened the retrieved citations, extracted relevant data, and assessed the risk of bias in the included trials, using the Cochrane Collaboration criteria modified by McMaster University and Methodological Index for Non-Randomized Studies (MINORS). We used a narrative synthesis to present the results. RESULTS: Ten studies (comprising 29 publications) met our inclusion criteria, including 8 randomized controlled trials and 2 uncontrolled trials. No severe adverse events associated with ADSC therapy were reported. While most efficacy endpoints did not reach statistical significance, there were reports of improved ischemic area, functional capacity, symptoms, and contractility in patients treated with ADSCs. CONCLUSIONS: The findings from our review suggest that ADSC therapy is generally safe for patients with ischemic heart disease. However, further investigation is warranted to confirm its efficacy, particularly with larger clinical trials and in specific conditions where improvements in microcirculation may have a notable impact on clinical outcomes.

FUNDAMENTO: A terapia celular utilizando células-tronco mesenquimais derivadas do tecido adiposo (ADSC, sigla em inglês) apresenta grande potencial como tratamento para doenças cardiovasculares. OBJETIVO: Realizamos uma revisão sistemática para descrever a segurança e a eficácia das ADSC na cardiopatia isquêmica. MÉTODOS: Pesquisamos na PubMed/MEDLINE, EMBASE, Web of Science, CENTRAL e LILACS (desde o início até março de 2024) por estudos clínicos envolvendo ADSC em pacientes com cardiopatia isquêmica. Excluímos estudos envolvendo pacientes com outros tipos de doenças cardíacas, estudos utilizando células-tronco mesenquimais derivadas de outros tecidos, bem como estudos em andamento. Dois revisores independentes realizaram a triagem das citações recuperadas, extraíram dados relevantes e avaliaram o risco de viés nos ensaios incluídos, utilizando os critérios da Colaboração Cochrane modificados pela Universidade McMaster e o Índice Metodológico para Estudos Não-Randomizados (MINORS). Utilizamos uma síntese narrativa para apresentar os resultados. RESULTADOS: Dez estudos (compreendendo 29 publicações) preencheram nossos critérios de inclusão, incluindo 8 ensaios controlados randomizados e 2 ensaios não controlados. Não foram relatados eventos adversos graves associados à terapia com ADSC. Embora a maioria dos desfechos de eficácia não tenha alcançado significância estatística, houve relatos de melhora da área isquêmica, capacidade funcional, sintomas e contratilidade em pacientes tratados com ADSC. CONCLUSÕES: Os resultados da nossa revisão sugerem que a terapia com ADSC é geralmente segura para pacientes com cardiopatia isquêmica. Contudo, são necessárias mais investigações para confirmar a sua eficácia, particularmente em ensaios clínicos de maior escala e em condições específicas onde as melhorias na microcirculação podem ter um impacto notável nos desfechos clínicos.

Gene Therapy: Targeting Cardiomyocyte Proliferation to Repopulate the Ischemic Heart.

ABSTRACT: Adult mammalian cardiomyocytes show scarce division ability, which makes the heart ineffective in replacing lost contractile cells after ischemic cardiomyopathy. In the past decades, there have been increasing efforts in the search for novel strategies to regenerate the injured myocardium. Among them, gene therapy is one of the most promising ones, based on recent and emerging studies that support the fact that functional cardiomyocyte regeneration can be accomplished by the stimulation and enhancement of the endogenous ability of these cells to achieve cell division. This capacity can be targeted by stimulating several molecules, such as cell cycle regulators, noncoding RNAs, transcription, and metabolic factors. Therefore, the proposed target, together with the selection of the vector used, administration route, and the experimental animal model used in the development of the therapy would determine the success in the clinical field.

Muerte súbita cardíaca por fibrilación ventricular asociada a isquemia miocárdica, tratada por desfibrilador automático implantable / Sudden cardiac death due to ventricular fibrillation associated with myocardial ischemia, treated by implantable cardioverter defibrillator

Resumen: Reportamos el caso de un hombre de 67 años, con múltiples factores de riesgo cardiovascular, quien en el año 2015 presentó muerte súbita por fibrilación ventricular sin lesiones coronarias significativas, tras lo cual se implantó un desfibrilador automático. En el año 2019 presentó un nuevo episodio de fibrilación ventricular en relación con síndrome coronario agudo con supradesnivel del ST localizado en pared anterior, registrado y adecuadamente resuelto por el dispositivo. Se demostró una oclusión aterotrombótica en la porción proximal de la arteria descendente anterior. Fue precoz y exitosamente manejado con angioplastía coronaria percutánea e implante de stent fármaco activo, guiado por tomografía por coherencia óptica intracoronaria. A las 48 horas post angioplastía, presentó episodio de taquicardia ventricular polimorfa reconocido y tratado por el cardiodesfibrilador, sin consecuencias. Electivamente se efectuó angioplastía e implante de stent metálico en arteria coronaria derecha distal, con buen resultado angiográfico. La posterior evolución del paciente fue satisfactoria, sin manifestaciones de insuficiencia cardíaca, angina ni arritmias.

Abstract: A 67-year-old man, with multiple cardiovascular risk factors who in 2015 presented sudden death due to ventricular fibrillation without significant coronary lesions, after which an implantable automatic defibrillator (ICD) was implanted. In 2019, he presented a new episode of ventricular fibrillation adequately resolved by the device, in relation to an acute coronary syndrome with ST elevation in the anterior wall of the left ventricle, due to atherothrombotic occlusion in the proximal portion of the anterior descending artery. He was early and successfully managed with percutaneous coronary angioplasty by the insertion of a drug eluting stent, implanted guided by intracoronary optical coherence tomography. Forty eight hours later, he presented an episode polymorphic ventricular tachycardia recognized and treated by the ICD. Angioplasty with a bare metal stent implantation were performed in the distal right coronary artery, with good angiographic results. The subsequent course was satisfactory, with no manifestations of heart failure, angina or arrhythmias.

Ischemia/Reperfusion Injury: Pathophysiology, Current Clinical Management, and Potential Preventive Approaches.

Myocardial ischemia reperfusion syndrome is a complex entity where many inflammatory mediators play different roles, both to enhance myocardial infarction-derived damage and to heal injury. In such a setting, the establishment of an effective therapy to treat this condition has been elusive, perhaps because the experimental treatments have been conceived to block just one of the many pathogenic pathways of the disease, or because they thwart the tissue-repairing phase of the syndrome. Either way, we think that a discussion about the pathophysiology of the disease and the mechanisms of action of some drugs may shed some clarity on the topic.

Effects of moderate and high intensity isocaloric aerobic training upon microvascular reactivity and myocardial oxidative stress in rats.

Systemic and central cardiovascular adaptations may vary in response to chronic exercise performed with different intensities and volumes. This study compared the effects of aerobic training with different intensities but equivalent volume upon microvascular reactivity in cremaster muscle and myocardial biomarkers of oxidative stress in Wistar rats. After peak oxygen uptake (VO2peak) assessment, rats (n = 24) were assigned into three groups: moderate-intensity exercise training (MI); high-intensity exercise training (HI); sedentary control (SC). Treadmill training occurred during 4 weeks, with exercise bouts matched by the energy expenditure (3.0-3.5 Kcal). Microvascular reactivity was assessed in vivo by intravital microscopy in cremaster muscle arterioles, while biomarkers of oxidative stress and eNOS expression were quantified at left ventricle and at aorta, respectively. Similar increasing vs. sedentary control group (SC) occurred in moderate intensity training group (MI) and high-intensity training group (HI) for endothelium-dependent vasodilation (10-4M: MI: 168.7%, HI: 164.6% vs. SC: 146.6%, P = 0.0004). Superoxide dismutase (SOD) (HI: 0.13 U/mg vs. MI: 0.09 U/mg and SC: 0.06 U/mg; P = 0.02), glutathione peroxidase (GPX) (HI: 0.00038 U/mg vs. MI: 0.00034 U/mg and SC: 0.00024 U/mg; P = 0.04), and carbonyl protein content (HI: 0.04 U/mg vs. MI: 0.03 U/mg and SC: 0.01 U/mg; P = 0.003) increased only in HI. No difference across groups was detected for catalase (CAT) (P = 0.12), Thiobarbituric acid reactive substances (TBARS) (P = 0.38) or eNOS expression in aorta (P = 0.44). In conclusion, higher exercise intensity induced greater improvements in myocardium antioxidant defenses, while gains in microvascular reactivity appeared to rely more on exercise volume than intensity.

Gene therapy for refractory angina and cell therapy for heart failure: experience of a Brazilian research group.

Cell therapy has shown impressive effects in experimental cardiomyopathy models. To a lesser extent, gene therapy has also been studied. In both cases, translation to clinical therapy has been disappointing. This paper is intended to describe the experience and achievements of a multicenter working group located in Porto Alegre, southern Brazil, in experimental and translational research projects for cell-based and gene therapy methods in the treatment of dilated and ischemic cardiomyopathies. The results of preclinical and clinical studies showed that bone marrow mononuclear stem cells indeed have an effect in improving myocardial perfusion and contractile function, but the overall results are poorly translated to the clinical level. Gene therapy studies with direct myocardial injections of naked VEGF 165 plasmid showed improvement in myocardial perfusion and function in animal models. A randomized clinical trial found that this method is safe and improved myocardial perfusion, but the benefits disappeared after 1 year. An animal experiment associating VEGF 165 with angiopoietin was undertaken in mini pigs to extend the durability of that therapy. In conclusion, our efforts to better understand the mechanisms and functions of gene and cell-based therapies in cardiology resulted in significant findings and propose a future look at cell-free therapeutic approaches.

Factores de riesgo coronario modificables en el servicio de enfermería del Hospital General Universitario Vladimir Ilich Lenin. Noviembre 2016-Noviembre 2018 / Modifiable coronary risk factors in the nursing service of the University General Hospital Vladimir Ilich Lenin. November 2016 - November 2018

La cardiopatía isquémica es la enfermedad más común, grave y de mayor riesgo en términos de mortalidad, morbilidad en gran parte del mundo, contribuyendo una serie de factores, que se relacionan con un riesgo aumentado de padecer dicha enfermedad. Se realizó un estudio transversal durante el período comprendido entre el 1ro de noviembre del 2016 al 1ro de noviembre del 2018 con el objetivo de contribuir al conocimiento de los factores de riesgo coronario modificables en enfermeros(as) del Hospital General Universitario Vladimir Ilich Lenin. Se trabajaron con variables principales: el tabaquismo, la obesidad, la hipertensión arterial, la diabetes mellitus, la dieta rica en grasas saturadas, la dislipidemia, el sedentarismo y la tensión emocional mantenida. El dato primario se obtuvo a través de la entrevista, el examen físico, y la determinación de lípidos en sangre. Se estudiaron variables sociodemográficas y biomédicas generales. Dentro de los factores de riesgo prevalecieron la tensión emocional mantenida 88,5 por ciento, la dieta rica en grasa saturada 86,0 por ciento y el sedentarismo para 82,0 por ciento. En un porcentaje menor se mostraron la obesidad 49,0 por ciento y la dislipidemia para 44,0 por ciento. Se destaca que en una importante proporción de casos coexistían dos y tres factores de riesgo a la vez. Es elevado el riesgo cardiovascular como consecuencia de la alta prevalencia de los factores de riesgo coronario encontrados(AU)

Ischemic heart disease is the most common disease, serious and most at risk in terms of mortality, morbidity in much of the world, contributing a number of factors, which are related to an increased risk of suffering from such disease. A cross-sectional study was conducted during the period from November 1, 2016 to November 1, 2018 with the objective of contributing to the knowledge of the modifiable coronary risk factors in nurses of the General University Hospital Vladimir Ilich Lenin. They worked with main variables: smoking, obesity, high blood pressure, diabetes mellitus, diet high in saturated fat, dyslipidemia, sedentary lifestyle and sustained emotional tension. The primary data was obtained through the interview, physical examination, and blood lipid determination. General sociodemographic and biomedical variables were studied. Among the risk factors, the emotional tension maintained 88.5 percent, the diet rich in saturated fat 86.0 percent and the sedentary lifestyle prevailed for 82.0 percent. In a smaller percentage, obesity was 49.0 percent and dyslipidemia for 44.0 percent. It is emphasized that in a significant proportion of cases two and three risk factors coexisted at the same time. The cardiovascular risk is high as a consequence of the high prevalence of the coronary risk factors found(EU)

Profile of the nursing diagnoses in stable heart disease patients.

OBJECTIVES: To identify the nursing diagnoses through reports in the medical records of patients monitored in a specialized ischemic heart disease outpatient clinic. METHODS: Cross-sectional study with retrospective data collection in the medical records. From the data collected, the nursing diagnoses were proposed by the researchers and submitted for validation by specialist cardiology nurses. RESULTS: A total of 13 nursing diagnoses were evaluated from the medical records of 50 outpatients with the following validation agreements among the specialists: Ineffective health management (100%), Noncompliance (100%), Sedentary lifestyle (100%), Activity intolerance (100%), Decreased cardiac output (88%), Risk of decreased cardiac tissue perfusion (65%), Risk of intolerance to activity (65%), Acute pain (76%), Ineffective health maintenance (65%), Risk-prone health behavior (65%), Risk for decreased cardiac output (65%), Risk for intolerance to activity (65%), Ineffective respiratory pattern (53%), Impaired memory (29%). CONCLUSIONS: In this study, the nursing diagnoses validated for stable heart disease patients were linked to adherence to treatment and to the cardiovascular responses of the patients, reinforcing the importance of early intervention. These results allow the multidisciplinary team to individualize the goals and interventions proposed for ischemic heart disease patients.

Recent Advances in Pharmacological and Non-Pharmacological Strategies of Cardioprotection.

Ischemic heart diseases (IHD) are the leading cause of death worldwide. Although the principal form of treatment of IHD is myocardial reperfusion, the recovery of coronary blood flow after ischemia can cause severe and fatal cardiac dysfunctions, mainly due to the abrupt entry of oxygen and ionic deregulation in cardiac cells. The ability of these cells to protect themselves against injury including ischemia and reperfusion (I/R), has been termed "cardioprotection". This protective response can be stimulated by pharmacological agents (adenosine, catecholamines and others) and non-pharmacological procedures (conditioning, hypoxia and others). Several intracellular signaling pathways mediated by chemical messengers (enzymes, protein kinases, transcription factors and others) and cytoplasmic organelles (mitochondria, sarcoplasmic reticulum, nucleus and sarcolemma) are involved in cardioprotective responses. Therefore, advancement in understanding the cellular and molecular mechanisms involved in the cardioprotective response can lead to the development of new pharmacological and non-pharmacological strategies for cardioprotection, thus contributing to increasing the efficacy of IHD treatment. In this work, we analyze the recent advances in pharmacological and non-pharmacological strategies of cardioprotection.

Comparação entre avaliação de isquemia miocárdica pela reserva de fluxo fracionada e cintilografia de perfusão miocárdica / Comparison between myocardial ischemia evaluation by fractional flow reserve and myocardial perfusion scintigraphy

Lesões coronárias moderadas podem ser, ou não, responsáveis pela isquemia miocárdica. A análise funcional das lesões pode ser realizada por métodos invasivos e não invasivos. Comparar a análise funcional das lesões coronarianas moderadas pela reserva de fluxo fracionado e pela cintilografia de perfusão miocárdica. Foram estudados prospectivamente 47 pacientes com doença arterial coronária estável com pelo menos uma lesão coronariana moderada obstrutiva. Eles foram submetidos à reserva de fluxo fracionado e à cintilografia de perfusão miocárdica com intervalo médio de 24,5 dias, entre janeiro de 2013 e dezembro de 2015. Não houve alteração no estado clínico e nem no procedimento de revascularização entre exames. As variáveis populacionais foram descritas como mediana e interquartil. A reserva de fluxo fracionado foi realizada em um de tronco de coronária esquerda; 37 artérias coronárias descendentes; 12 artérias circunflexas e quatro artérias coronárias direitas. Reserva de fluxo fracionado < 0,8 foi considerada positiva. A análise comparativa entre os resultados dos testes foi feita pelo teste de Fisher bicaudal, sendo considerado significativo valor de p < 0,05. A reserva de fluxo fracionado < 0,8 foi encontrada no tronco de coronária esquerda (100%); 13 na artéria coronária descendente (35,14%); seis na artéria circunflexa (50%) e duas na artéria coronária direita (50%). Dentre os pacientes com reserva de fluxo fracionado positiva, 83% tinham isquemia miocárdica demonstrada na cintilografia de perfusão miocárdica (p = 0,058). Analisando especificamente o território da artéria coronária descendente, 83% dos pacientes com reserva de fluxo fracionado negativa não tinham isquemia na cintilografia de perfusão miocárdica, mas 69% dos pacientes com reserva de fluxo fracionado positiva não tinham isquemia na cintilografia de perfusão miocárdica (p = 0,413). Pode ocorrer discordância entre os resultados de análise funcional de lesões coronárias moderadas por testes invasivos e não invasivos

Moderate coronary artery lesions can be, or not, responsible for myocardial ischemia. The functional analysis of these lesions can be performed by invasive and noninvasive methods.To compare the functional analysis of moderate coronary lesions by fractional flow reserve and myocardial perfusion scintigraphy. 47 patients with stable coronary artery disease and at least one moderate coronary artery obstruction were prospectively studied. They were submitted to fractional flow reserve and myocardial perfusion scintigraphy with a median interval of 24.5 days between January 2013 and December 2015. There was no change in clinical status or revascularization procedure between the exams. The population variables were described as medians and interquartile range. Fractional flow reserve was performed in one left main coronary artery; 37 left descending coronary arteries; 12 circumflex arteries and 4 right coronary arteries. Fractional flow reserve < 0.8 was considered positive. The comparative analysis between the results of the tests was performed by two-tailed Fisher's test and a p-value 0.05 was considered significant.Fractional flow reserve < 0.8 was found in the left main coronary artery (100%); 13 in the left descending coronary artery (35.14%); 6 in circumflex artery (50%) and 2 in the right coronary artery (50%). Among the patients with positive fractional flow reserve, 83% had myocardial ischemia demonstrated by the myocardial perfusion scintigraphy (p = 0.058).When analyzing specifically the left descending coronary artery, 83% of the patients with negative fractional flow reserve showed no ischemia at the myocardial perfusion scintigraphy, but 69% of the patients with positive fractional flow reserve showed no ischemia at the myocardial perfusion scintigraphy (p = 0.413). Disagreements can occur between the results of the functional analysis of moderate coronary lesions by invasive and noninvasive tests

Loss-Framed Financial Incentives and Personalized Goal-Setting to Increase Physical Activity Among Ischemic Heart Disease Patients Using Wearable Devices: The ACTIVE REWARD Randomized Trial.

BACKGROUND: Regular physical activity reduces the risk of cardiovascular events, but most ischemic heart disease (IHD) patients do not obtain enough. METHODS AND RESULTS: ACTIVE REWARD (A Clinical Trial Investigating Effects of a Randomized Evaluation of Wearable Activity Trackers with Financial Rewards) was a 24-week home-based, remotely monitored, randomized trial with a 16-week intervention (8-week ramp-up incentive phase and 8-week maintenance incentive phase) and an 8-week follow-up. Patients used wearable devices to track step counts and establish a baseline. Patients in control received no other interventions. Patients in the incentive arm received personalized step goals and daily feedback for all 24 weeks. In the ramp-up incentive phase, daily step goals increased weekly by 15% from baseline with a maximum of 10 000 steps and then remained fixed. Each week, $14 was allocated to a virtual account; $2 could be lost per day for not achieving step goals. The primary outcome was change in mean daily steps from baseline to the maintenance incentive phase. Ischemic heart disease patients had a mean (SD) age of 60 (11) years and 70% were male. Compared with control, patients in the incentive arm had a significantly greater increase in mean daily steps from baseline during ramp-up (1388 versus 385; adjusted difference, 1061 [95% confidence interval, 386-1736]; P<0.01), maintenance (1501 versus 264; adjusted difference, 1368 [95% confidence interval, 571-2164]; P<0.001), and follow-up (1066 versus 92; adjusted difference, 1154 [95% confidence interval, 282-2027]; P<0.01). CONCLUSIONS: Loss-framed financial incentives with personalized goal setting significantly increased physical activity among ischemic heart disease patients using wearable devices during the 16-week intervention, and effects were sustained during the 8-week follow-up. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02531022.

The homing of bone marrow stem cells is differentially activated in ischemic and valvular heart diseases and influenced by beta-blockers.

BACKGROUND: Cell homing is the mechanism by which an injury releases signaling molecules that cause recruitment, proliferation, migration and differentiation of progenitor cells. Stromal derived factor-1 (SDF-1) and its receptor CXCR4 are key molecules involved in homing and little is known about their activation in cardiopathies. Here, we assessed the homing activation status of bone marrow cells (BMC) concerning the SDF-1 and CXCR4 expression in ischemic (IHD) and valvular (VHD) heart diseases. METHODS: The SDF-1 and inflammatory profile were analyzed by ELISA from plasma obtained bone marrow of ischemic heart patients (IHD, n = 41), valvular heart patients (VHD, n = 30) and healthy controls (C, n = 9). Flow cytometry was used to evaluate CXCR4 (CD184) expression on the surface of bone marrow cells, and the CXCR4 expression was estimated by real-time quantitative PCR. RESULTS: The SDF-1 levels in the groups IHD, VHD and control were, respectively, 230, 530 and 620 pg/mL (P = 0.483), and was decreased in VHD patients using beta-blockers (263 pg/mL) when compared with other (844 pg/mL) (P = 0.023). Compared with IHD, the VHD group showed higher CXCR4 (P = 0.071) and CXCR7 (P = 0.082) mRNA expression although no difference in the level of CXCR4+ bone marrow cells was found between groups (P = 0.360). CONCLUSION: In conclusion, pathophysiological differences between IHD and VHD can affect the molecules involved in the activation of homing. In addition, the use of beta-blockers appears to interfere in this mechanism, a fact that should be considered in protocols that use BMC.

Relato de caso sobre comunicação interventricular pós-infarto agudo do miocárdio / Case report on acute postinfarction myocardial interventricular septal rupture

O presente artigo relata dois casos de pacientes, os quais foram admitidos na emergência do Instituto de Moléstias Cardiovasculares (IMC) com dor tipicamente anginosa, caracterizada como dor retroesternal em aperto, com irradiação para a face medial do braço esquerdo e relacionada ao esforço, com melhora no repouso. No exame físico, apresentavam taquicardia e sudorese. O eletrocardiograma evidenciou sinais de isquemia miocárdica em ambos os pacientes. Após as medidas iniciais serem tomadas, um dos pacientes foi submetido à terapia trombolítica e o outro à angioplastia para implantação de stent . Mais tarde, foi identificada a comunicação interventricular (CIV), seguido da necessidade de correção cirúrgica da mesma. Ambos os pacientes evoluíram bem, apesar da alta taxa de mortalidade desta condição

This paper reports two cases of patients who were admitted to the emergency room of the Instituto de Moléstias Cardiovasculares (IMC) with typically anginal pain, characterized by tight retrosternal pain radiating to the inside left arm, related to stress and improving with rest. Physical examination showed tachycardia and excessive sweating. Electrocardiogram showed signs of myocardial ischemia in both patients. After the initial measures were taken, one of the patients received thrombolytic therapy, and the other angioplasty for stent implantation. Later, interventricular septum rupture (IVSR) was identified, followed by the need for surgery to correct it. Both patients recovered well, despite the high mortality rate of this condition

Ischemic left ventricle systolic dysfunction: An evidence-based approach in diagnostic tools and therapeutics.

Coronary artery disease (CAD) associated with left ventricular systolic dysfunction is a condition related to poor prognosis. There is a lack of robust evidence in many aspects related to this condition, from definition to treatment. Ischemic cardiomyopathy is a spectrum ranging from stunned myocardium associated with myocardial fibrosis to hibernating myocardium and repetitive episodes of ischemia. In clinical practice, relevance lies in identifying the myocardium that has the ability to recover its contractile reserve after revascularization. Methods to evaluate cellular integrity tend to have higher sensitivity, while the ones assessing contractile reserve have greater specificity, since a larger mass of viable myocytes is required in order to generate contractility change. Since there are many methods and different ways to detect viability, sensitivity and specificity vary widely. Dobutamine-cardiac magnetic resonance with late gadolinium enhancement has the best accuracy is this setting, giving important predictors of prognostic and revascularization benefit such as scar burden, contractile reserve and end-systolic volume index. The latter has shown differential benefit with revascularization in some recent trials. Finally, authors discuss interventional procedures in this population, focusing on coronary artery bypass grafting and evolution of evidence from CASS to post-STICH era.

Increased Hazard of Myocardial Infarction With Insulin-Provision Therapy in Actively Smoking Patients With Diabetes Mellitus and Stable Ischemic Heart Disease: The BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) Trial.

BACKGROUND: In the BARI 2D (Bypass Angioplasty Revascularization Investigation 2 Diabetes) trial, randomization of diabetic patients with stable ischemic heart disease to insulin provision (IP) therapy, as opposed to insulin sensitization (IS) therapy, resulted in biochemical evidence of impaired fibrinolysis but no increase in adverse clinical outcomes. We hypothesized that the prothrombotic effect of IP therapy in combination with the hypercoagulable state induced by active smoking would result in an increased risk of myocardial infarction (MI). METHODS AND RESULTS: We analyzed BARI 2D patients who were active smokers randomized to IP or IS therapy. The primary end point was fatal or nonfatal MI. PAI-1 (plasminogen activator inhibitor 1) activity was analyzed at 1, 3, and 5 years. Of 295 active smokers, MI occurred in 15.4% randomized to IP and in 6.8% randomized to IS over the 5.3 years (P=0.023). IP therapy was associated with a 3.2-fold increase in the hazard of MI compared with IS therapy (hazard ratio: 3.23; 95% confidence interval, 1.43-7.28; P=0.005). Baseline PAI-1 activity (19.0 versus 17.5 Au/mL, P=0.70) was similar in actively smoking patients randomized to IP or IS therapy. However, IP therapy resulted in significantly increased PAI-1 activity at 1 year (23.0 versus 16.0 Au/mL, P=0.001), 3 years (24.0 versus 18.0 Au/mL, P=0.049), and 5 years (29.0 versus 15.0 Au/mL, P=0.004) compared with IS therapy. CONCLUSIONS: Among diabetic patients with stable ischemic heart disease who were actively smoking, IP therapy was independently associated with a significantly increased hazard of MI. This finding may be explained by higher PAI-1 activity in active smokers treated with IP therapy. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00006305.

Ischemic left ventricle systolic dysfunction: An evidence-based approach in diagnostic tools and therapeutics / Miocardiopatia isquêmica: uma abordagem diagnóstica e terapêutica baseada em evidências

Summary Coronary artery disease (CAD) associated with left ventricular systolic dysfunction is a condition related to poor prognosis. There is a lack of robust evidence in many aspects related to this condition, from definition to treatment. Ischemic cardiomyopathy is a spectrum ranging from stunned myocardium associated with myocardial fibrosis to hibernating myocardium and repetitive episodes of ischemia. In clinical practice, relevance lies in identifying the myocardium that has the ability to recover its contractile reserve after revascularization. Methods to evaluate cellular integrity tend to have higher sensitivity, while the ones assessing contractile reserve have greater specificity, since a larger mass of viable myocytes is required in order to generate contractility change. Since there are many methods and different ways to detect viability, sensitivity and specificity vary widely. Dobutamine-cardiac magnetic resonance with late gadolinium enhancement has the best accuracy is this setting, giving important predictors of prognostic and revascularization benefit such as scar burden, contractile reserve and end-systolic volume index. The latter has shown differential benefit with revascularization in some recent trials. Finally, authors discuss interventional procedures in this population, focusing on coronary artery bypass grafting and evolution of evidence from CASS to post-STICH era.

Resumo A doença arterial coronariana (DAC) associada à disfunção sistólica do ventrículo esquerdo é uma condição relacionada a mau prognóstico. Há uma falta de evidência robusta em muitos aspectos relacionados a essa condição, desde a definição ao tratamento. A cardiomiopatia isquêmica é um espectro que varia de miocárdio atordoado por fibrose miocárdica, passando por miocárdio hibernante, a episódios repetitivos de isquemia. Na prática clínica, a importância do problema é identificar o miocárdio que tem a capacidade de recuperar sua reserva contrátil após revascularização. Métodos para avaliar a integridade celular tendem a ter maior sensibilidade, enquanto os que avaliam a reserva contrátil têm maior especificidade, uma vez que uma maior massa de miócitos viáveis para gerar uma mudança de contratilidade é necessária. Tendo em vista que existem muitos métodos e diferentes formas de detecção de viabilidade, a sensibilidade e a especificidade variam amplamente. O uso da ressonância magnética cardíaca com detecção de realce tardio associada a estresse com dobutamina tem a melhor acurácia na avaliação de viabilidade, além de fornecer importantes preditores de benefício prognóstico com a revascularização, tais como carga de cicatriz, reserva contrátil e índice de volume sistólico final. Finalmente, os autores discutem sobre procedimentos intervencionistas nessa população, com foco na revascularização cirúrgica do miocárdio e na evolução da evidência desde o estudo CASS até os trials da era pós-STICH.