Diabetic cardiomyopathy: factual or factoid?

SUMMARY Although long ago described, there is no established consensus regarding the real existence of Diabetic Cardiomyopathy (CMPDM). Due to its complex pathophysiology, it has been difficult for clinical and experimental research to establish clear connections between diabetes mellitus (DM) and heart failure (HF), as well as to solve the mechanisms of the underlying myocardial disease. However, the epidemiological evidence of the relationship of these conditions is undisputed. The interest in understanding this disease has intensified due to the recent results of clinical trials evaluating new glucose-lowering drugs, such as sodium-glucose transporter inhibitors 2, which demonstrated favorable responses considering the prevention and treatment of HF in patients with DM. In this review we cover aspects of the epidemiology of CMPDM and its possible pathogenic mechanisms, as well as, present the main cardiac phenotypes of CMPDM (HF with preserved and reduced ejection fraction) and implications of the therapeutic management of this disease.

RESUMO Apesar de há muito tempo descrita, não existe consenso estabelecido quanto à real existência da cardiomiopatia diabética (CMPDM). Devido à sua complexa fisiopatologia, tem sido árduo à pesquisa clínica e experimental estabelecer conexões claras entre diabetes mellitus (DM) e insuficiência cardíaca (IC), assim como solucionar os mecanismos da doença subjacente do miocárdio. No entanto, as evidências epidemiológicas da relação dessas condições são incontestáveis. O interesse em compreender melhor essa doença tem recrudescido devido aos recentes resultados de ensaios clínicos avaliando novos fármacos hipoglicemiantes, como os inibidores do transportador de sódio-glicose 2, que demonstraram respostas favoráveis, considerando-se a prevenção e tratamento da IC em pacientes portadores de DM. Nesta revisão, percorremos aspectos da epidemiologia da CMPDM e de seus possíveis mecanismos patogênicos, além de apresentarmos os principais fenótipos cardíacos da CMPDM (IC com fração de ejeção preservada e reduzida) e implicações do manejo terapêutico desta doença.

Cardiomiopatía diabética / Diabetic cardiomyopathy

La enfermedad coronaria, la hipertensión arterial y la diabetes son factores de riesgo independientes para el desarrollo de insuficiencia cardíaca y muerte. La cardiomiopatía diabética (CMD) es una de las etiologías frecuentes de cardiopatía en pacientes con diabetes tipo 1 y tipo 2. Si bien se suele plantear la CMD como la causa de la cardiopatía cuando se excluyen la hipertensión arterial, las valvulopatías y la enfermedad arterial coronaria aterotrombótica, estas coexisten con frecuencia e incluso también con la neuropatía autónoma cardiovascular. En los pacientes con CMD se puede demostrar mediante tests serológicos y por imagen alteraciones a nivel molecular, metabólico, mitocondrial, celular y tisular con infiltración grasa del músculo cardíaco, vinculadas a hiperglicemia, hiperinsulinemia y resistencia a la insulina, así como a lipotoxicidad por ácidos grasos libres, que son responsables del desarrollo de la CMD. Esta entidad primero determina disfunción diastólica del ventrículo izquierdo, más tarde disfunción sistólica e insuficiencia cardíaca. Se diagnostica mediante estudios serológicos de marcadores biológicos múltiples y por técnicas de imagen que evidencian la disfunción ventricular y mejoran la predicción pronóstica de enfermedad cardiovascular en diabéticos. En base a dichas pruebas se ha propuesto una clasificación por estadios o fenotipos clínicos de la CMD, que apunta a su diagnóstico precoz. Puede ser asintomática o ser responsable de síntomas y manifestaciones severas tales como insuficiencia cardíaca, arritmias y muerte súbita. Se puede asociar a hipertensión arterial, a enfermedad coronaria, a otras manifestaciones de microangiopatía y macroangiopatía aterotrombótica y a mortalidad cardiovascular. La prevención y el tratamiento intensivo multifactorial y personalizado de la diabetes, de todas sus alteraciones metabólicas y de la cardiopatía, mejoran la calidad y prolongan la vida. Se espera que investigaciones recientes, en proceso y futuras, determinen portentosos avances en la prevención y en el tratamiento de la CMD, que constituye una de las serias amenazas a la salud de la humanidad.

Coronary heart disease, hypertension and diabetes mellitus are independent risk factors for heart failure and death. Diabetic cardiomyopathy (DCM) is one of the common etiologies of cardiac disease in patients with diabetes type 1 or 2. Although DCM is often considered as the cause of heart disease when arterial hypertension, valvulopathies and atherothrombotic coronary artery are excluded, they coexist frequently, as well as with cardiovascular neuropathy. In patients with DCM, serological and imaging tests can show alterations at the molecular, metabolic, mitochondrial, cellular and tissue levels with fatty infiltration of the heart muscle, linked to hyperglycemia, hyperinsulinemia, insulin resistance, and lipotoxicity by fatty free acids, which are responsible for the development of the cardiomyopathy. The DCM first determines left ventricular diastolic dysfunction, later systolic dysfunction and heart failure. It is diagnosed by serological tests of multiple biological markers and by imaging tests that demonstrate ventricular dysfunction and improve the prognostic prediction of cardiovascular disease in diabetics. Based on these tests, a classification by stages or clinical phenotypes of DCM, which aims at its early diagnosis, has been proposed. It can be asymptomatic or be responsible for symptoms and severe manifestations such as heart failure, arrhythmias and sudden death, and may associate hypertension, coronary disease, other manifestations of microangiopathy and atherothrombotic macroangiopathy and cardiovascular mortality. The prevention and intensive multifactorial and personalized treatment of diabetes and all its metabolic and cardiac alterations, improve quality and prolong life. It is expected that ongoing and future research will determine breakthroughs in the prevention and treatment of DCM, which is one of the serious threats to the health of mankind.

Intravenous administration of bone marrow-derived multipotent mesenchymal stromal cells has a neutral effect on obesity-induced diabetic cardiomyopathy

Obesity is a major global health issue. Obese patients develop metabolic syndrome, which is a cluster of clinical features characterized by insulin resistance and dyslipidemia. Its cardiac manifestation, diabetic cardiomyopathy, leads to heart failure. Bone marrow-derived multipotent mesenchymal stromal cells, also referred to as mesenchymal stem cells (MSC) are envisioned as a therapeutic tool not only for cardiovascular diseases but also for other degenerative conditions. Our aim was to evaluate whether the intravenous administration of MSC modifies cardiac dysfunction in obese mice. To this end, C57BL/6 mice were fed a regular (normal) or high-fat diet (obese). Obese animals received the vehicle (obese), a single dose (obese + 1x MSC) or three doses (obese + 3x MSC) of 0.5x10(6) syngeneic MSC. Two to three months following MSC administration, cardiac function was assessed by cardiac catheterization, at basal condition and after a pharmacological stress. Compared to normal mice, obese mice presented hyperglycemia, hyperinsulinemia, hypercholesterolemia and cardiac dysfunction after stress condition. Exogenous MSC neither improved nor impaired this cardiac dysfunction. Thus, intravenous administration of MSC has neutral effect on obesity-induced diabetic cardiomyopathy.

Cirugía de revascularización miocárdica versus angioplastía coronaria con stent en enfermedad de tres vasos y/o tronco común izquierdo en diabéticos: meta-análisis de estudios aleatorios / Meta-analysis of coronary artery bypass surgery compared to percutaneous transluminal angioplasty with stent in diabetic patients

Background: Diabetic patients are a group of primary interest in the study of myocardial revascularization. Aim: To compare coronary artery bypass grafting surgery (CABG) and percutaneous angioplasty with stents (PCI-S) in diabetic patients with coronary three-vessel or left main coronary artery disease. Material and Methods: Meta-analysis of MEDLINE randomized controlled studies comparing CABG and PCI-S in diabetic patients. The primary outcome measure was major adverse cardiovascular events (MACCE), death, myocardial infarction, cerebrovascular accident (CVA) and coronary re-intervention. Secondary outcomes were the individual components of MACCE. Results: Three studies comparing CABG and PCI-S met the inclusion criteria. One thousand sixty two patients were studied: 565 in the CABG group and 597 in the PCI-S group. At one year follow up MACCE occurred in 24.9 and 12.7% of patients in PCI-S and CABG groups, respectively (Odds ratio (OR) 2.27; 95% confidence intervals (CI) 1.66-3.09). There were no differences in death or myocardial infarction. Strokes were less common in the PCI-S group (OR 0.25, 95% CI0.09-0.68) and coronary re-intervention was required with higher frequency in the PCI-S group (OR 5.32, 95% CI 3.27-8.67). Conclusions: In diabetic patients with three-vessel coronary disease or left main coronary artery, revascularization with CABG had significantly less MACCE at one year than those treated with PCI-S. Stroke frequency was higher in CABG, coronary re-intervention was higher in PCI-S. These results must be interpreted cautiously.