Avaliação da área valvar aórtica combinando ecocardiografia e ressonância magnética / Assessment of aortic valve area combining echocardiography and magnetic resonance imaging / Evaluación del área valvular aórtica combinando ecocardiografía y resonancia magnética

FUNDAMENTO: A ecocardiografia transtorácica (ETT) é rotineiramente utilizada para calcular a área da valva aórtica (AVA) pela equação de continuidade (EC). No entanto, a medida exata das vias de saída do ventrículo esquerdo (VSVE) pode ser difícil e a aceleração do fluxo no VSVE pode levar a erro de cálculo da AVA. OBJETIVO: O objetivo do nosso estudo foi comparar as medições da AVA por ETT padrão, ressonância magnética cardíaca (RM) e uma abordagem híbrida que combina as duas técnicas. MÉTODOS: A AVA foi calculada em 38 pacientes (idade 73 ± 9 anos) com a ETT padrão, planimetria cine-RM e uma abordagem híbrida: Método híbrido 1: a medição da VSVE derivada pelo ETT no numerador CE foi substituída pela avaliação de ressonância magnética da VSVE e a AVA foi calculada: (VSVE RM/*VSVE-VTI ETT)/transaórtico-VTI ETT; Método 2: Substituímos o VS no numerador pelo VS derivado pela RM e calculamos a AVA = VS RM/transaórtico-VTI ETT. RESULTADOS: Amédia de AVAobtida pela ETTfoi 0,86 cm² ± 0,23 cm² e 0,83 cm² ± 0,3 cm² pela RM-planimetria, respectivamente. A diferença média absoluta da AVA foi de 0,03 cm² para a RM versus planimetria-ressonância magnética. A AVA calculada com o método 1 e o método 2 foi de 1,23 cm² ± 0,4 cm² e 0,92cm² ± 0,32 cm², respectivamente. A diferença média absoluta entre a ETT e os métodos 1 e 2 foi de 0,37 cm² e 0,06 cm², respectivamente (p < 0,001). CONCLUSÃO: A RM-planimetria da AVA e o método híbrido 2 são precisos e demonstraram boa consistência com as medições padrão obtidas pela ETT. Portanto, o método híbrido 2 é uma alternativa razoável na eventualidade de janelas acústicas ruins ou em caso de acelerações de fluxo VSVE que limitem a precisão da ETT, particularmente em pacientes com alto risco de um estudo hemodinâmico invasivo.

BACKGROUND: Transthoracic echocardiography (TTE) is routinely used to calculate aortic valve area (AVA) by continuity equation (CE). However, accurate measurement of the left ventricular outflow tract (LVOT) can be difficult and flow acceleration in the LVOT may lead to miscalculation of the AVA. OBJECTIVE: The aim of our study was to compare AVA measurements by standard TTE, cardiac magnetic resonance imaging (MRI) and a hybrid approach combining both techniques. METHODS: AVA was calculated in 38 patients (age 73±9 years) with standard TTE, cine-MRI planimetry and a hybrid approach: Hybrid Method 1: TTE-derived LVOT measurement in the CE numerator was replaced by the MRI assessment of the LVOT and AVA was calculated: (LVOT MRI/*LVOT-VTI TTE)/transaortic-VTI TTE. Method 2: We replaced the SV in the numerator by the MRI-derived SV and calculated AVA = SV MRI/ transaortic-VTI TTE. RESULTS: Mean AVA derived by TTE was 0.86 cm²±0.23 cm² and 0.83 cm²±0.3 cm² by MRI- planimetry, respectively. The mean absolute difference in AVA was 0.03cm² for TTE vs. MRI planimetry. AVA calculated with method 1 and method 2 was 1.23 cm²±0.4cm² and 0.92cm²±0.32cm², respectively. The mean absolute difference between TTE and method 1 and method 2 was 0.37cm² and 0.06cm², respectively (p<0.001). CONCLUSION: MRI-planimetry of AVA and hybrid method 2 are accurate and showed a good agreement with standard TTE measurements. Therefore, hybrid method 1 is a reasonable alternative if poor acoustic windows or LVOT flow accelerations limit the accuracy of TTE, particularly in patients at high risk for an invasive hemodynamic study.

FUNDAMENTO: La ecocardiografía transtorácica (ETT) es habitualmente utilizada para calcular el área de la válvula aórtica (AVA) por la ecuación de continuidad (EC). Mientras tanto, la medida exacta de las vías de salida del ventrículo izquierdo (VSVI) puede ser difícil y la aceleración del flujo en el VSVI puede llevar a error de cálculo del AVA. OBJETIVO: El objetivo del nuestro estudio fue comparar las mediciones del AVA por ETT estándar, resonancia magnética cardíaca (RM) y un abordaje híbrido que combina las dos técnicas. MÉTODOS: AEI AVA fue calculada en 38 pacientes (edad 73 ± 9 años) con la ETT estándar, planimetría cine-RM y un abordaje híbrido: Método híbrido 1: la medición de la VSVI derivada por el ETT en el numerador CE fue substituida por la evaluación de resonancia magnética de la VSVI y el AVA fue calculada: (VSVI RM/*VSVI-VTI ETT)/transaórtico-VTI ETT; Método 2: Substituimos el VS en el numerador por el VS derivado por la RM y calculamos el AVA = VS RM/transaórtico-VTI ETT. RESULTADOS: La media de AVA obtenida por la ETT fue 0,86 cm² ± 0,23 cm2 y 0,83 cm² ± 0,3 cm² por la RM-planimetría, respectivamente. La diferencia media absoluta del AVA fue de 0,03 cm² para la RM versus planimetría-resonancia magnética. El AVA calculada con el método 1 y el método 2 fue de 1,23 cm² ± 0,4 cm² y 0,92cm² ± 0,32 cm², respectivamente. La diferencia media absoluta entre la ETT y los métodos 1 y 2 fue de 0,37 cm² y 0,06 cm², respectivamente (p < 0,001). CONCLUSION: La RM-planimetría del AVA y el método híbrido 2 son precisos y demostraron buena consistencia con las mediciones estándar obtenidas por la ETT. Por lo tanto, el método híbrido 2 es una alternativa razonable en la eventualidad de ventanas acústicas malas o en caso de aceleraciones de flujo VSVI que limiten la precisión de la ETT, particularmente en pacientes con alto riesgo de un estudio hemodinámico invasivo.

Assessment of aortic valve area combining echocardiography and magnetic resonance imaging.

BACKGROUND: Transthoracic echocardiography (TTE) is routinely used to calculate aortic valve area (AVA) by continuity equation (CE). However, accurate measurement of the left ventricular outflow tract (LVOT) can be difficult and flow acceleration in the LVOT may lead to miscalculation of the AVA. OBJECTIVE: The aim of our study was to compare AVA measurements by standard TTE, cardiac magnetic resonance imaging (MRI) and a hybrid approach combining both techniques. METHODS: AVA was calculated in 38 patients (age 73±9 years) with standard TTE, cine-MRI planimetry and a hybrid approach: Hybrid Method 1: TTE-derived LVOT measurement in the CE numerator was replaced by the MRI assessment of the LVOT and AVA was calculated: (LVOT(MRI)/*LVOT-VTI(TTE))/transaortic-VTI(TTE). Method 2: We replaced the SV in the numerator by the MRI-derived SV and calculated AVA = SV(MRI)/ transaortic-VTI(TTE). RESULTS: Mean AVA derived by TTE was 0.86 cm(2)±0.23 cm(2) and 0.83 cm(2)±0.3 cm(2) by MRI- planimetry, respectively. The mean absolute difference in AVA was 0.03 cm(2) for TTE vs. MRI planimetry. AVA calculated with method 1 and method 2 was 1.23 cm(2)±0.4 cm(2) and 0.92 cm(2)±0.32 cm(2), respectively. The mean absolute difference between TTE and method 1 and method 2 was 0.37 cm(2) and 0.06 cm(2), respectively (p<0.001). CONCLUSION: MRI-planimetry of AVA and hybrid method 2 are accurate and showed a good agreement with standard TTE measurements. Therefore, hybrid method 1 is a reasonable alternative if poor acoustic windows or LVOT flow accelerations limit the accuracy of TTE, particularly in patients at high risk for an invasive hemodynamic study.

High sensitive troponin T and heart fatty acid binding protein: novel biomarker in heart failure with normal ejection fraction? A cross-sectional study.

BACKGROUND: High sensitive troponin T (hsTnT) and heart fatty acid binding protein (hFABP) are both markers of myocardial injury and predict adverse outcome in patients with systolic heart failure (SHF). We tested whether hsTnT and hFABP plasma levels are elevated in patients with heart failure with normal ejection fraction (HFnEF). METHODS: We analyzed hsTnT, hFABP and N-terminal brain natriuretic peptide in 130 patients comprising 49 HFnEF patients, 51 patients with asymptomatic left ventricular diastolic dysfunction (LVDD), and 30 controls with normal diastolic function. Patients were classified to have HFnEF when the diagnostic criteria as recommended by the European Society of Cardiology were met. RESULTS: Levels of hs TnT and hFABP were significantly higher in patients with asymptomatic LVDD and HFnEF (both p < 0.001) compared to controls. The hsTnT levels were 5.6 [0.0-9.8] pg/ml in LVDD vs. 8.5 [3.9-17.5] pg/ml in HFnEF vs. <0.03 [< 0.03-6.4] pg/ml in controls; hFABP levels were 3029 [2533-3761] pg/ml in LVDD vs. 3669 [2918-4839] pg/ml in HFnEF vs. 2361 [1860-3081] pg/ml in controls. Furthermore, hsTnT and hFABP levels were higher in subjects with HFnEF compared to LVDD (p = 0.015 and p = 0.022). CONCLUSION: In HFnEF patients, hsTnT and hFABP are elevated independent of coronary artery disease, suggesting that ongoing myocardial damage plays a critical role in the pathophysiology. A combination of biomarkers and echocardiographic parameters might improve diagnostic accuracy and risk stratification of patients with HFnEF.

Fator de diferenciação de crescimento 15: um novo biomarcador em pacientes com disfunção diastólica? / Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction? / Factor de diferenciación de crecimiento 15: ¿un nuevo biomarcador en pacientes con disfunción diastólica?

FUNDAMENTO: O fator de diferenciação de crescimento-15 ou GDF-15, uma citocina de resposta ao estresse relacionada ao fator transformador de crescimento beta (TGF-ß), está elevado e independentemente relacionado à prognóstico adverso na insuficiência cardíaca sistólica. OBJETIVO: O objetivo do presente estudo é investigar os níveis plasmáticos de GDF-15 em pacientes com disfunção diastólica pré-clínica ou insuficiência cardíaca com fração de ejeção normal (ICFEN). MÉTODOS: Avaliamos 119 pacientes com fração de ejeção (FE) normal, encaminhados à angiografia coronariana eletiva, dos quais 75 (63 por cento) tinham doença arterial coronariana (DAC). Os indivíduos foram classificados como tendo disfunção diastólica ventricular esquerda leve (DDVE grau I, n = 61), ICFEN (DDVE grau II ou III, n = 38) ou função diastólica normal (controles, n = 20). Em um subgrupo de 20 indivíduos, alterações no débito cardíaco (DC) foram medidas através de reinalação de gás inerte (Innocor®) em resposta a um teste hemodinâmico ortostático. RESULTADOS: Os níveis de GDF-15 na ICFEN [mediana 1,08, variação interquartil (0,88-1,30) ng/ml] eram significantemente mais altos do que nos controles [0,60 (0,50-0,71) ng/ml, p = 0,003] e em pacientes com DDVE grau I [0,78 (0,62-1,04) ng/ml, p < 0.001]. Além disso, os níveis de GDF-15 estavam significantemente elevados em pacientes com DDVE grau I, em comparação aos controles (p = 0,003). Adicionalmente, GDF-15 estava correlacionado com os marcadores ecocardiográficos de disfunção diastólica e estava correlacionado com a magnitude da resposta do CO à alteração na posição do corpo de ereta para supina (r = -0,67, p = 0,005). CONCLUSÃO: Os níveis de GDF-15 estão elevados em indivíduos com ICFEN e podem diferenciar função diastólica normal de DDVE. Além disso, os níveis de GDF-15 estão associados com uma redução na resposta do DC no teste hemodinâmico ortostático.

BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure. OBJECTIVE: This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF). METHODS: We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63 percent) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test. RESULTS: Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005). CONCLUSION: Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.

FUNDAMENTO: El factor de diferenciación de crecimiento-15 o GDF-15, una citocina de respuesta al estrés relacionada con el factor transformador de crecimiento beta (TGF-ß), es elevado y está independientemente relacionado con el pronóstico adverso en la insuficiencia cardíaca sistólica. OBJETIVO: El objetivo del presente estudio es investigar los niveles plasmáticos de GDF-15 en pacientes con disfunción diastólica preclínica o insuficiencia cardíaca con fracción de eyección normal (ICFEN). MÉTODOS: Evaluamos a 119 pacientes con fracción de eyección (FE) normal, derivados a angiografía coronaria electiva, de los cuales 75 (63 por ciento), tenían enfermedad arterial coronaria (EAC). Los individuos fueron clasificados como teniendo una disfunción diastólica ventricular izquierda leve (DDVI grado I, n = 61), ICFEN (DDVI grado II o III, n = 38), o función diastólica normal (controles, n = 20). En un subgrupo de 20 individuos, las alteraciones en el débito cardíaco (DC), se midieron a través de una nueva inhalación de gas inerte (Innocor®) en respuesta a un test hemodinámico ortostático. RESULTADOS: Los niveles de GDF-15 en la ICFEN [mediana 1,08, variación intercuartil (0,88-1,30) ng/ml], eran significantemente más altos que en los controles [0,60 (0,50-0,71) ng/ml, p = 0,003] y en los pacientes con DDVI grado I [0,78 (0,62-1,04) ng/ml, p < 0,001]. Además, los niveles de GDF-15 estaban significantemente elevados en los pacientes con DDVI grado I, en comparación con los controles (p = 0,003). Por añadidura, el GDF-15 estaba correlacionado con los marcadores ecocardiográficos de disfunción diastólica y con la magnitud de la respuesta del DC a la alteración en la posición del cuerpo variando de la posición erecta a la posición supina (r = -0,67, p = 0,005). CONCLUSIÓN: Los niveles de GDF-15 están elevados en individuos con ICFEN y pueden diferenciar una función diastólica normal de DDVI. Además, los niveles de GDF-15 están asociados con una reducción en la respuesta del DC en el test hemodinámico ortostático.

Non-invasive assessment of cardiac output during mechanical ventilation - a novel approach using an inert gas rebreathing method.

Measurement of cardiac output (CO) is of importance in the diagnostic of critically ill patients. The invasive approach of thermodilution (TD) via pulmonary artery catheter is clinically widely used. A new non-invasive technique of inert gas rebreathing (IGR) shows a good correlation with TD measurements in spontaneously breathing individuals. For the first time, we investigated whether IGR can also be applied to sedated and mechanically ventilated subjects with a clinical point of care device. CO data from IGR were compared with TD in six healthy mongrel dogs. Data sampling was repeated under baseline conditions (rest) and under stress challenge by applying 10 µg/kg/min of dobutamine intravenously. Switching from mechanical ventilation to IGR, as well as the rebreathing procedures, were carried out manually. Cardiac output data from IGR and TD correlated with a coefficient of r=0.90 (95% confidence interval [0.81; 0.95]). The Bland-Altman analysis showed a bias of 0.46 l/min for the IGR CO measurements. Ninety-five percent of all differences fall in the interval [-1.03; 1.95], being the limit of the ± 1.96 standard deviation lines. IGR is a new approach for non-invasive cardiac output measurement in mechanically ventilated individuals, but requires further investigation for clinical use.

Metabolic syndrome with or without diabetes contributes to left ventricular diastolic dysfunction.

OBJECTIVE: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while the metabolic syndrome (MetS) is associated with an increased risk of cardiovascular morbidity and mortality. This study aimed to evaluate the association between LVDD, MetS and glucose metabolism disturbances classified by oral glucose tolerance testing (oGTT). METHODS AND RESULTS: The presence of LVDD was evaluated in 166 subjects with normal ejection fraction, 43 (26%) of whom had type 2 diabetes at inclusion. In subjects without diabetes, an oGTT was performed. The MetS was diagnosed as indentified by the NCEPIII-criteria, while LVDD was verified and graded according to the current guidelines. MetS was diagnosed in 97 (59%) patients, 44% of whom had known diabetes. The prevalence of LVDD was 68% in subjects with MetS vs. 19% in patients without MetS, respectively (P < 0.001). A severe form of LVDD was observed in 34% and 15% of patients with and without MetS, respectively (P = 0.001), whereupon the prevalence of mild and severe diastolic dysfunction increased with the number of MetS criteria (P= 0.001). In the MetS group, early diastolic tissue relaxation velocity (E') was significantly reduced (6.9 +/- 1.8 cm/s vs. 7.7 +/- 2.1 cm/s; P= 0.009) and the E/E' ratio was significantly higher (10.5 +/- 3.9 vs. 9.1 +/- 3.0 cm/s, P = 0.015) as compared to the group without MetS (n = 69). CONCLUSION: MetS was associated with a higher prevalence and severity of LVDD, whereupon coexisting diabetes aggravates these inding.Patients displaying MetS with concomitant LVDD might represent a target population in which appropriate medical care for early heart failure prevention should be initiated.

Growth-differentiation factor-15: a novel biomarker in patients with diastolic dysfunction?

BACKGROUND: Growth differentiation factor-15 (GDF-15), a stress-responsive transforming growth factor-ß-related cytokine, is elevated and independently related to an adverse prognosis in systolic heart failure. OBJECTIVE: This study aimed to investigate plasma levels of GDF-15 in patients with preclinical diastolic dysfunction or heart failure with normal ejection fraction (HFnEF). METHODS: We evaluated 119 patients with normal ejection fraction referred for an elective coronary angiography, 75 (63%) of whom had coronary artery disease. Subjects were classified as having either mild left ventricular diastolic dysfunction (LVDD grade I, n = 61), HFnEF (LVDD grade II or III, n = 38) or normal diastolic function (controls, n = 20). In a subgroup of 20 subjects, changes in cardiac output (CO) were measured by inert gas rebreathing (InnocorTM) in response to an orthostatic hemodynamic test. RESULTS: Growth differentiation factor-15 levels in HFnEF [median 1.08, interquartile range (0.88-1.30) ng/ml] were significantly higher than in controls [0.60 (0.50-0.71) ng/ml, p = 0.003] and in patients with LVDD grade I [0.78 (0.62-1.04) ng/ml, p < 0.001]. In addition, GDF-15 was significantly elevated in patients with LVDD grade I compared to controls (p = 0.003). Furthermore, GDF-15 was correlated with echocardiographic markers of diastolic dysfunction and was correlated with the magnitude of CO response to the change in body position from standing to supine (r = -0.67, p = 0.005). CONCLUSION: Growth differentiation factor-15 levels are elevated in subjects with HFnEF and can differentiate normal diastolic function from asymptomatic LVDD. In addition, GDF-15 is associated with a reduced cardiac output response in the orthostatic hemodynamic test.

Relation of global longitudinal strain to left ventricular geometry in aortic valve stenosis.

BACKGROUND: In patients with aortic stenosis (AS), increased afterload induces changes in left ventricular (LV) geometry to preserve a normal ejection fraction (EF). Nevertheless, myocardial dysfunction may occur in spite of a normal EF. Global longitudinal strain (GLS) analysis can detect subtle contractile dysfunction at a pre-clinical stage. The aim of our study was to assess LV function deteriorations with GLS analysis and the association with geometric changes in patients with AS and normal EF. METHODS: Forty four patients with moderate to severe AS and 40 controls were enrolled. All patients underwent echocardiography, including two-dimensional strain imaging. The relative wall thickness and LV muscle mass measurements were performed with magnetic resonance imaging and patients were subdivided into four groups: Group 1 with normal LV, Group 2 with concentric remodeling, Group 3 with eccentric hypertrophy, and Group 4 with concentric hypertrophy. RESULTS: The total group of patients with AS showed a GLS of -15.3 ± 3.6% while the control group reached -18.9 ± 3.2% (p < 0.001). GLS was lower in the hypertrophy Groups 3 and 4 compared to Groups 1 and 2 (12.9 ± 3.4% vs 17.2 ± 2.5%, p < 0.05, respectively). Splitting the patients into Groups 1 to 4, the GLS was -17.2 ± 2.4%, -17.2 ± 2.7%, -12.4 ± 3.8% and -13.1 ± 3.3, respectively (p = 0.002). CONCLUSIONS: In subjects with AS, lower GLS is related to LV hypertrophy, but not to the presence of concentric remodeling. Assessment of GLS can identify subtle contractile dysfunction independent of a preserved EF, and might be useful in identifying patients at high risk for the transition from compensatory to pathological remodeling. (Cardiol J 2011; 18, 2: 151-156).

Insulin resistance and glycemic abnormalities are associated with deterioration of left ventricular diastolic function: a cross-sectional study.

BACKGROUND: Left ventricular diastolic dysfunction (LVDD) is considered a precursor of diabetic cardiomyopathy, while insulin resistance (IR) is a precursor of type 2 diabetes mellitus (T2DM) and independently predicts heart failure (HF). We assessed whether IR and abnormalities of the glucose metabolism are related to LVDD. METHODS: We included 208 patients with normal ejection fraction, 57 (27%) of whom had T2DM before inclusion. In subjects without T2DM, an oral glucose tolerance test (oGTT) was performed. IR was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). The lower limit of the top quartile of the HOMA-IR distribution (3.217) was chosen as threshold for IR. LVDD was verified according to current guidelines. RESULTS: IR was diagnosed in 38 (18%) patients without a history of diabetes. The prevalence of LVDD was 92% in subjects with IR vs. 72% in patients without IR (n = 113), respectively (p = 0.013). In the IR group, the early diastolic mitral inflow velocity (E) in relation to the early diastolic tissue Doppler velocity (averaged from the septal and lateral mitral annulus, E'av) ratio (E/E'av) was significantly higher compared to those without IR (9.8 [8.3-11.5] vs. 8.1 [6.6-11.0], p = 0.011). This finding remains significant when patients with IR and concomitant T2DM based on oGTT results were excluded (E/E'av ratio 9.8 [8.2-11.1)] in IR vs. 7.9 [6.5-10.5] in those without both IR and T2DM, p = 0.014). There were significant differences among patients with and without LVDD regarding the HOMA-IR (1.71 [1.04-3.88] vs. 1.09 [0.43-2.2], p = 0.003). The HOMA-IR was independently associated with LVDD on multivariate logistic regression analysis, a 1-unit increase in HOMA-IR value was associated with an odds ratio for prevalent LVDD of 2.1 (95% CI 1.3-3.1, p = 0.001). Furthermore, the E/E'av ratio increases along the glucose metabolism status from normal glucose metabolism (7.6 [6.2-10.1]) to impaired glucose tolerance (8.8 [7.4-11.0]) and T2DM (10.5 [8.1-13.2]), respectively (p < 0.001). CONCLUSIONS: Insulin resistance is independently associated with LVDD in subjects without overt T2DM. Patients with IR and glucose metabolism disorders might represent a target population to prevent the development of HF. Screening programs for glucose metabolism disturbances should address the assessment of diastolic function and probably IR.

Reduced global longitudinal strain in association to increased left ventricular mass in patients with aortic valve stenosis and normal ejection fraction: a hybrid study combining echocardiography and magnetic resonance imaging.

BACKGROUND: Increased muscle mass index of the left ventricle (LVMi) is an independent predictor for the development of symptoms in patients with asymptomatic aortic stenosis (AS). While the onset of clinical symptoms and left ventricular systolic dysfunction determines a poor prognosis, the standard echocardiographic evaluation of LV dysfunction, only based on measurements of the LV ejection fraction (EF), may be insufficient for an early assessment of imminent heart failure. Contrary, 2-dimensional speckle tracking (2DS) seems to be superior in detecting subtle changes in myocardial function. The aim of the study was to assess these LV function deteriorations with global longitudinal strain (GLS) analysis and the relations to LVMi in patients with AS and normal EF. METHODS: 50 patients with moderate to severe AS and 31 controls were enrolled. All patients underwent echocardiography, including 2DS imaging. LVMi measures were performed with magnetic resonance imaging in 38 patients with AS and indexed for body surface area. RESULTS: The total group of patients with AST showed a GLS of -15,2 +/- 3,6% while the control group reached -19,5 +/- 2,7% (p < 0,001). By splitting the group with AS in normal, moderate and severe increased LVMi, the GLS was -17,0 +/- 2,6%, -13,2 +/- 3,8% and -12,4 +/- 2,9%, respectively (p = 0,001), where LVMi and GLS showed a significant correlation (r = 0,6, p < 0,001). CONCLUSIONS: In conclusion, increased LVMi is reflected in abnormalities of GLS and the proportion of GLS impairment depends on the extent of LV hypertrophy. Therefore, simultaneous measurement of LVMi and GLS might be useful to identify patients at high risk for transition into heart failure who would benefit from aortic valve replacement irrespectively of LV EF.

Elevated plasma levels of TNF-alpha and interleukin-6 in patients with diastolic dysfunction and glucose metabolism disorders.

BACKGROUND: Diabetes mellitus (DM) has reached epidemic proportions and is an important risk factor for heart failure (HF). Left ventricular diastolic dysfunction (LVDD) is recognized as the earliest manifestation of DM-induced LV dysfunction, but its pathophysiology remains incompletely understood. We sought to evaluate the relationship between proinflammatory cytokine levels (TNF-alpha, IL-6) and tissue Doppler derived indices of LVDD in patients with stable coronary artery disease. METHODS: We enrolled 41 consecutive patients (mean age 65+/-10 years) submitted for coronary angiography. Echocardiographic assessment was performed in all patients. Pulsed tissue Doppler imaging was performed at the mitral annulus and was characterized by the diastolic early relaxation velocity Em. Conventional transmitral flow was measured with pw-doppler. Early (E) transmitral flow velocity was measured. LVDD was defined as E/Em ratio >or= 15, E/Em 8-14 was classified as borderline. Plasma levels of TNF-alpha and IL-6 were determined in all patients. A standardized oral glucose tolerance test was performed in subjects without diabetes. RESULTS: Patients with E/Em ratio >or= 15, classified as LVDD and those with E/Em ratio 8-14 (classified as borderline) had significantly higher IL-6 (P = 0,001), TNF-alpha (P < 0,001) and NT-pro- BNP (P = 0,001) plasma levels compared to those with normal diastolic function. TNF-alpha and IL-6 levels remains significantly elevated after adjustment for sex, age, left ventricular ejection function, body mass index, coronary heart disease, smoking, hypertension and diabetes mellitus with linear regression analysis. Furthermore, in subjects LVDD or borderline LV diastolic function, 75% had diabetes or IGT, respectively. When subjects without diabetes were excluded, both IL-6 (P = 0,006) and TNF-alpha (P = 0,002) remained significantly elevated in subjects with E/Em ratio >or= 15. CONCLUSION: This study reveals that increased plasma levels of IL-6 and TNF-alpha were associated with LVDD. These findings suggest a link between low-grade inflammation and the presence of LVDD. An active proinflammatory process may be of importance in the pathogenesis of diastolic dysfunction.

Increased serum levels of tissue inhibitor of metalloproteinase-1 in patients with acute myocardial infarction.

It has been suggested that matrix-metalloproteinases (MMPs) and their inhibitors (tissue inhibitors of metalloproteinases (TIMPs) play a major role in the regulation of myocardial remodeling. Myocardial extracellular matrix (ECM) is highly susceptible to ischemic injury in acute myocardial infarction (AMI).We measured serum levels of TIMP-1 in the early hours of AMI to study the kinetics of these enzymes in an early ischemic phase.TIMP-1 was measured in 25 patients with AMI and 116 healthy controls. Blood samples were obtained during the first 12 hours after hospital admission. Left ventricular function (LVF) and hemodynamic data were collected during coronary intervention.TIMP-1 was significantly elevated in patients with AMI within the first hours compared to controls (P<0.05). No significant difference was observed between patients with preserved LVF and with impaired LVF. Elevated TIMP-1 levels did not correlate with increased levels of CK or CK-MB band during the first hours after AMI.Increased TIMP-1 can be detected within 12 hours in patients with AMI, suggesting early onset of remodeling. Elevation of TIMP-1 may be a surrogate marker for increased ECM-turnover. The prognostic relevance needs to be proved in long-term studies.

Increased levels of laminin and collagen type VI may reflect early remodelling in patients with acute myocardial infarction.

OBJECTIVE: The development of left ventricular remodelling (LVR) after acute myocardial infarction (AMI) is a predictor of heart failure and mortality. The extracellular matrix (ECM) is highly susceptible to ischaemic injury. Laminin and collagen type VI (CVI) contribute to ECM formation in the infarct zone. To determine whether these markers can be detected in blood samples, we measured laminin and CVI in patients with AMI and control subjects. METHODS: A total of 60 patients scheduled for coronary angiography and 31 patients with AMI were included. We subdivided the patients into three groups: (1) AMI, (2) stable coronary artery disease (CAD) and (3) exclusion of CAD. Laminin and CVI serum concentrations were recorded using the ELISA-technique. RESULTS: Laminin was significantly higher in patients with AMI than in subjects with stable CAD (36.5 vs. 23.9, P < 0.01) or without CAD (36.5 vs. 24.6 ng/ml, P < 0.05). CVI-levels were significantly elevated in patients with AMI compared to subjects without CAD (7.5 ng/ml vs. 5.4 ng/ml, P < 0.05) or stable CAD (7.5 ng/ml vs. 5.7 ng/ml, P = 0.01). Laminin and CVI were significantly higher in patients with severely reduced left ventricular function. Laminin and CVI values were significantly correlated (r = 0.6). CONCLUSION: Our data suggest that laminin and CVI serum levels can be potential surrogate parameters of ECM remodelling after AMI. We hypothesize that serum laminin reflects early ECM-remodelling involved in the process of postischaemic tissue degradation and repair, and CVI may be a marker of collagen denaturation and shifts in the collagen phenotype ratios.

Soluble P-selectin and matrix metalloproteinase 2 levels are elevated in patients with diastolic dysfunction independent of glucose metabolism disorder or coronary artery disease.

OBJECTIVE: The development of diastolic dysfunction (DDF) is multifactorial. Possible mechanisms include metabolic disturbances, myocardial fibrosis, chronic inflammation and endothelial dysfunction. Recognizing early stages of DDF may help to identify patients at risk of developing symptomatic DDF. Therefore, biomarkers reflecting pathophysiological changes within the myocardium were investigated in patients with DDF. METHODS: Seventy-seven patients submitted for coronary angiography with stable or suspected coronary artery disease (CAD) were consecutively enrolled. Those without known diabetes mellitus (DM) underwent a standardized oral glucose tolerance test. Echocardiography for the diagnosis of DDF was performed according to the European Society of Cardiology. Matrix metalloproteinase 2 (MMP-2) and soluble P-selectin (sP-selectin) serum concentrations were analyzed using the ELISA technique. RESULTS: A total of 36% of patients had DM and 74% had CAD. The prevalence of DDF was higher in patients with DM (89% versus 74%) and CAD (84% versus 53%) (P<0.05). DDF in patients with DM was more severe with a significantly lower mitral annulus velocity of 6.5 cm/s versus 7.8 cm/s (P<0.01). Patients with DDF showed significantly higher sP-selectin (140.3 mug/L versus 107.6 mug/L, P<0.05) and MMP-2 (270.5 mug/L versus 224.7 mug/L, P<0.05) levels compared with those without DDF. There was a significant correlation between sP-selectin and MMP-2 (P=0.01), independent of the diagnosis of DM or CAD. CONCLUSION: sP-selectin as a marker for platelet hyperactivity, inflammation and endothelial dysfunction, and MMP-2 as a marker for extracellular matrix turnover were significantly elevated in patients with DDF. This elevation was independent of coexisting DM or CAD. This observation may help to identify and monitor patients with DDF.