Post-Mortem Cardiac 3T Magnetic Resonance Imaging. Visualization of Sudden Cardiac Death?

OBJECTIVES: This study aimed to investigate post-mortem magnetic resonance imaging (pmMRI) for the assessment of myocardial infarction and hypointensities on post-mortem T2-weighted images as a possible method for visualizing the myocardial origin of arrhythmic sudden cardiac death. BACKGROUND: Sudden cardiac death has challenged clinical and forensic pathologists for decades because verification on post-mortem autopsy is not possible. pmMRI as an autopsy-supporting examination technique has been shown to visualize different stages of myocardial infarction. METHODS: In 136 human forensic corpses, a post-mortem cardiac MR examination was carried out prior to forensic autopsy. Short-axis and horizontal long-axis Images were acquired in situ on a 3-T system. RESULTS: In 76 cases, myocardial findings could be documented and correlated to the autopsy findings. Within these 76 study cases, a total of 124 myocardial lesions were detected on pmMRI (chronic: 25; subacute: 16; acute: 30; and peracute: 53). Chronic, subacute, and acute infarction cases correlated excellently to the myocardial findings on autopsy. Peracute infarctions (age range: minutes to approximately 1 h) were not visible on macroscopic autopsy or histological examination. Peracute infarction areas detected on pmMRI could be verified in targeted histological investigations in 62.3% of cases and could be related to a matching coronary finding in 84.9%. A total of 15.1% of peracute lesions on pmMRI lacked a matching coronary finding but presented with severe myocardial hypertrophy or cocaine intoxication facilitating a cardiac death without verifiable coronary stenosis. CONCLUSIONS: 3-T pmMRI visualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarction as a possible cause of sudden cardiac death, it demonstrates affected myocardial areas not visible on autopsy. pmMRI should be considered as a feasible post-mortem investigation technique for the deceased patient if no consent for a clinical autopsy is obtained.

Cirrhotic cardiomyopathy: A cardiologist’s perspective

Cardiac dysfunction is frequently observed in patients with cirrhosis, and has long been linked to the direct toxic effect of alcohol. Cirrhotic cardiomyopathy (CCM) has recently been identified as an entity regardless of the cirrhosis etiology. Increased cardiac output due to hyperdynamic circulation is a pathophysiological hallmark of the disease. The underlying mechanisms involved in pathogenesis of CCM are complex and involve various neurohumoral and cellular pathways, including the impaired β-receptor and calcium signaling, altered cardiomyocyte membrane physiology, elevated sympathetic nervous tone and increased activity of vasodilatory pathways predominantly through the actions of nitric oxide, carbon monoxide and endocannabinoids. The main clinical features of CCM include attenuated systolic contractility in response to physiologic or pharmacologic strain, diastolic dysfunction, electrical conductance abnormalities and chronotropic incompetence. Particularly the diastolic dysfunction with impaired ventricular relaxation and ventricular filling is a prominent feature of CCM. The underlying mechanism of diastolic dysfunction in cirrhosis is likely due to the increased myocardial wall stiffness caused by myocardial hypertrophy, fibrosis and subendothelial edema, subsequently resulting in high filling pressures of the left ventricle and atrium. Currently, no specific treatment exists for CCM. The liver transplantation is the only established effective therapy for patients with end-stage liver disease and associated cardiac failure. Liver transplantation has been shown to reverse systolic and diastolic dysfunction and the prolonged QT interval after transplantation. Here, we review the pathophysiological basis and clinical features of cirrhotic cardiomyopathy, and discuss currently available limited therapeutic options.

Myocardial injection of skeletal myoblasts impairs contractility of host cardiomyocytes

BACKGROUND: Mechanisms underlying improvement of myocardial contractile function after cell therapy as well as arrhythmic side effect remain poorly understood. We hypothesised that cell therapy might affect the mechanical properties of isolated host cardiomyocytes. METHODS: Two weeks after myocardial infarction (MI), rats were treated by intramyocardial myoblast injection (SkM, n=8), intramyocardial vehicle injection (Medium, n=6), or sham operation (Sham, n=7). Cardiac function was assessed by echocardiography. Cardiomyocytes were isolated in a modified Langendorff perfusion system, their contraction was measured by video-based inter-sarcomeric analysis. Data were compared with a control-group without myocardial infarction (Control, n=5). RESULTS: Three weeks post-treatment, ejection fraction (EF) further deteriorated in vehicle-injected and non-injected rats (respectively 40.7+/-11.4% to 33+/-5.5% and 41.8+/-8% to 33.5+/-8.3%), but was stabilised in SkM group (35.9+/-6% to 36.4+/-9.7%). Significant cell hypertrophy induced by MI was maintained after cell therapy. Single cell contraction (dL/dt(max)) decreased in SkM and vehicle groups compared to non-injected group as well as cell shortening and relaxation (dL/dt(min)) in vehicle group. A significantly increased predisposition for alternation of strong and weak contractions was observed in isolated cardiomyocytes of the SkM group. CONCLUSION: Our study provides the first evidence that injection of materials into the myocardium alters host cardiomyocytes contractile function independently of the global beneficial effect of the heart function. These findings may be important in understanding possible adverse effects.

Right ventricular absolute myocardial blood flow in complex congenital heart disease

A consequence in patients with d-transposition of the great arteries (d-TGA) and tetralogy of Fallot (TOF) is right ventricular hypertrophy (RVH) and right ventricular failure. Myocardial contrast echocardiography (MCE) permits the determination of the myocardial microvascular density reflected by the relative myocardial blood volume (rBV; ml/ml). This study was conducted to elucidate the relationship between RVH and myocardial microvascular changes by quantitative MCE in patients with d-TGA and TOF.

The relative myocardial blood volume differentiates between hypertensive heart disease and athlete's heart in humans

AIMS: The adaptation of the myocardial microcirculation in humans to pathologic and physiologic stress has not been examined in vivo so far. We sought to test whether the relative blood volume (rBV) measured by myocardial contrast echocardiography (MCE) can differentiate between left ventricular (LV) hypertrophy (LVH) in hypertensive heart disease and athlete's heart. METHODS AND RESULTS: Four groups were investigated: hypertensive patients with LVH (n = 15), semi-professional triathletes with LVH (n = 15), professional football players (n = 15), and sedentary control individuals without cardiovascular disease (n = 15). MCE was performed at rest and during adenosine-induced hyperaemia. The rBV (mL mL(-1)), its exchange frequency (beta, min(-1)), and myocardial blood flow (mL min(-1) g(-1)) were derived from steady state and refill sequences of ultrasound contrast agent. Hypertensive patients had lower rBV (0.093 +/- 0.013 mL mL(-1)) than triathletes (0.141 +/- 0.012 mL mL(-1), P < 0.001), football players (0.129 +/- 0.014 mL mL(-1), P < 0.001), and sedentary individuals (0.126 +/- 0.018 mL mL(-1), P < 0.001). Conversely, the exchange frequency (beta) was significantly higher in hypertensive patients (11.3 +/- 3.8 min(-1)) than in triathletes (7.4 +/- 1.8 min(-1)), football players (7.7 +/- 2.3 min(-1)), and sedentary individuals (9.0+/-2.5 min(-1)). An rBV below 0.114 mL mL(-1) distinguished hypertensive patients and triathletes with a sensitivity of 93% and a specificity of 100%. CONCLUSION: Pathologic and physiologic LVH were differentiated non-invasively and accurately by rBV, a measure of vascularisation assessed by MCE.

The effect of a myocardial infarction on the normalized time-varying elastance curve

It has been suggested that the shape of the normalized time-varying elastance curve [E(n)(t(n))] is conserved in different cardiac pathologies. We hypothesize, however, that the E(n)(t(n)) differs quantitatively after myocardial infarction (MI). Sprague-Dawley rats (n = 9) were anesthetized, and the left anterior descending coronary artery was ligated to provoke the MI. A sham-operated control group (CTRL) (n = 10) was treated without the MI. Two months later, a conductance catheter was inserted into the left ventricle (LV). The LV pressure and volume were measured and the E(n)(t(n)) derived. Slopes of E(n)(t(n)) during the preejection period (alpha(PEP)), ejection period (alpha(EP)), and their ratio (beta = alpha(EP)/alpha(PEP)) were calculated, together with the characteristic decay time during isovolumic relaxation (tau) and the normalized elastance at end diastole (E(min)(n)). MI provoked significant LV chamber dilatation, thus a loss in cardiac output (-33%), ejection fraction (-40%), and stroke volume (-30%) (P < 0.05). Also, it caused significant calcium increase (17-fold), fibrosis (2-fold), and LV hypertrophy. End-systolic elastance dropped from 0.66 +/- 0.31 mmHg/microl (CTRL) to 0.34 +/- 0.11 mmHg/microl (MI) (P < 0.05). Normalized elastance was significantly reduced in the MI group during the preejection, ejection, and diastolic periods (P < 0.05). The slope of E(n)(t(n)) during the alpha(PEP) and beta were significantly altered after MI (P < 0.05). Furthermore, tau and end-diastolic E(min)(n) were both significantly augmented in the MI group. We conclude that the E(n)(t(n)) differs quantitatively in all phases of the heart cycle, between normal and hearts post-MI. This should be considered when utilizing the single-beat concept.

Myocardial contrast echocardiography for the distinction of hypertrophic cardiomyopathy from athlete's heart and hypertensive heart disease

BACKGROUND: Myocardial contrast echocardiography (MCE) is able to measure in vivo relative blood volume (rBV, i.e., capillary density), and its exchange frequency b, the constituents of myo-cardial blood flow (MBF, ml min-1 g-1). This study aimed to assess, by MCE, whether left ventricular hypertrophy (LVH) in hypertrophic cardiomyopathy (HCM) can be differentiated from LVH in triathletes (athlete's heart, AH) or from hypertensive heart disease patients (HHD). METHODS: Sixty individuals, matched for age (33 +/- 10 years) and gender, and subdivided into four groups (n = 15) were examined: HCM, AH, HHD and a group of sedentary individuals without LVH (S). rBV (ml ml-1), b (min-1) and MBF, at rest and during adenosine-induced hyperaemia, were derived by MCE in mid septal, lateral and inferior regions. The ratio of MBF during hyperaemia and MBF at rest yielded myocardial blood flow reserve (MBFR). RESULTS: Septal wall rBV at rest was lower in HCM (0.084 +/- 0.023 ml ml-1) than in AH (0.151 +/- 0.024 ml ml-1, p <0.01) and in S (0.129 +/- 0.026 ml ml-1, p <0.01), but was similar to HHD (0.097 +/- 0.016 ml ml-1). Conversely, MBFR was lowest in HCM (1.67 +/- 0.93), followed by HHD (2.8 +/- 0.93, p <0.01), by S (3.36 +/- 1.03, p <0.001) and by AH (4.74 +/- 1.46, p <0.0001). At rest, rBV <0.11 ml ml-1 accurately distinguished between HCM and AH (sensitivity 99%, specificity 99%), similarly MBFR < or =1.8 helped to distinguish between HCM and HHD (sensitivity 100%, specificity 77%). CONCLUSIONS: rBV at rest, most accurately distinguishes between pathological LVH due to HCM and physiological, endurance-exercise induced LVH.

Relaxation in hypertrophic cardiomyopathy and hypertensive heart disease: relations between hypertrophy and diastolic function

AIM To determine the relation between the extent and distribution of left ventricular hypertrophy and the degree of disturbance of regional relaxation and global left ventricular filling. METHODS Regional wall thickness (rWT) was measured in eight myocardial regions in 17 patients with hypertrophic cardiomyopathy, 12 patients with hypertensive heart disease, and 10 age matched normal subjects, and an asymmetry index calculated. Regional relaxation was assessed in these eight regions using regional isovolumetric relaxation time (rIVRT) and early to late peak filling velocity ratio (rE/A) derived from Doppler tissue imaging. Asynchrony of rIVRT was calculated. Doppler left ventricular filling indices were assessed using the isovolumetric relaxation time, the deceleration time of early diastolic filling (E-DT), and the E/A ratio. RESULTS There was a correlation between rWT and both rIVRT and rE/A in the two types of heart disease (hypertrophic cardiomyopathy: r = 0.47, p < 0.0001 for rIVRT; r = -0.20, p < 0.05 for rE/A; hypertensive heart disease: r = 0.21, p < 0.05 for rIVRT; r = -0.30, p = 0.003 for rE/A). The degree of left ventricular asymmetry was related to prolonged E-DT (r = 0. 50, p = 0.001) and increased asynchrony (r = 0.42, p = 0.002) in all patients combined, but not within individual groups. Asynchrony itself was associated with decreased E/A (r = -0.39, p = 0.01) and protracted E-DT (r = 0.69, p < 0.0001) and isovolumetric relaxation time (r = 0.51, p = 0.001) in all patients. These correlations were still significant for E-DT in hypertrophic cardiomyopathy (r = 0.56, p = 0.02) and hypertensive heart disease (r = 0.59, p < 0.05) and for isovolumetric relaxation time in non-obstructive hypertrophic cardiomyopathy (n = 8, r = 0.87, p = 0.005). CONCLUSIONS Non-invasive ultrasonographic examination of the left ventricle shows that in both hypertrophic cardiomyopathy and hypertensive heart disease, the local extent of left ventricular hypertrophy is associated with regional left ventricular relaxation abnormalities. Asymmetrical distribution of left ventricular hypertrophy is indirectly related to global left ventricular early filling abnormalities through regional asynchrony of left ventricular relaxation.

A-kinase anchoring protein Lbc coordinates a p38 activating signaling complex controlling compensatory cardiac hypertrophy

In response to stress, the heart undergoes a remodeling process associated with cardiac hypertrophy that eventually leads to heart failure. A-kinase anchoring proteins (AKAPs) have been shown to coordinate numerous prohypertrophic signaling pathways in cultured cardiomyocytes. However, it remains to be established whether AKAP-based signaling complexes control cardiac hypertrophy and remodeling in vivo. In the current study, we show that AKAP-Lbc assembles a signaling complex composed of the kinases PKN, MLTK, MKK3, and p38α that mediates the activation of p38 in cardiomyocytes in response to stress signals. To address the role of this complex in cardiac remodeling, we generated transgenic mice displaying cardiomyocyte-specific overexpression of a molecular inhibitor of the interaction between AKAP-Lbc and the p38-activating module. Our results indicate that disruption of the AKAP-Lbc/p38 signaling complex inhibits compensatory cardiomyocyte hypertrophy in response to aortic banding-induced pressure overload and promotes early cardiac dysfunction associated with increased myocardial apoptosis, stress gene activation, and ventricular dilation. Attenuation of hypertrophy results from a reduced protein synthesis capacity, as indicated by decreased phosphorylation of 4E-binding protein 1 and ribosomal protein S6. These results indicate that AKAP-Lbc enhances p38-mediated hypertrophic signaling in the heart in response to abrupt increases in the afterload.

Association Between Posttraumatic Stress Disorder Following Myocardial Infarction and Liver Enzyme Levels: A Prospective Study

Research in rodents demonstrated that psychological stress increases circulating levels of alanine transaminase, aspartate transaminase, and alkaline phosphatase reflecting liver injury. Moreover, chronic posttraumatic stress disorder and transaminases predicted coronary heart disease.

Inflammatory Biomarkers in Patients with Posttraumatic Stress Disorder Caused by Myocardial Infarction and the Role of Depressive Symptoms

Inflammation might link posttraumatic stress disorder (PTSD) with an increased risk of cardiovascular events. We explored the association between PTSD and inflammatory biomarkers related to cardiovascular morbidity and the role of co-morbid depressive symptoms in this relationship.

Stress hormones in patients with posttraumatic stress disorder caused by myocardial infarction and role of comorbid depression

Chronic posttraumatic stress disorder (PTSD) has been associated with perturbed hypothalamic-pituitary-adrenal (HPA) axis function and a hyperadrenergic state. We hypothesized that patients with PTSD attributable to myocardial infarction (MI) would show peripheral hypocortisolemia and increased norepinephrine levels, whereby taking into account that depressive symptoms would affect this relationship.

Patent arterial duct, bottle-meal, and fatal myocardial ischaemia

A patent arterial duct in pre-term neonates is frequent. Systemic complications consecutive to left-to-right shunting are well known but fatal myocardial ischaemia has not been described till now. The presented premature baby died from catecholamine refractory cardiogenic shock. Autoptic examination revealed acute ischaemic changes predominantly in the inner third of myocardium, speaking of coronary hypoperfusion due to a steal phenomenon secondary to the patent arterial duct.

Eotaxin/CCL11 levels correlate with myocardial fibrosis and mast cell density in native and transplanted rat hearts

Myocardial fibrosis contributes to hemodynamic and cardiac functional alterations commonly observed posttransplantation. Cardiac mast cells (MC) have been linked to fibrosis in posttransplantation hearts. Eotaxin, which has been shown to be involved in fibrogenesis, has been demonstrated to be increased in production in cardiac macrophages. The aim of our study was to correlate myocardial fibrosis during heart transplant rejection in the rat with eotaxin/chemokine [c-c motif] ligand 11 (CCL11) expression, and with various subtypes of infiltrating cardiac MC, namely connective-type MC (CTMC) and mucosa-type MC (MMC).

[Myocardial dysfunction in sepsis]

Myocardial dysfunction appears in 25% of patients with severe sepsis and in 50% of patients with septic shock, even in the presence of hyper dynamic states. It is characterized by a reduction in left ventricle ejection fraction, that reverts at the seventh to tenth day of evolution. Right ventricular dysfunction and diastolic left ventricular dysfunction can also appear. There is no consensus if an increase in end diastolic volume is part of the syndrome. High troponin or brain natriuretic peptide levels are associated with myocardial dysfunction and a higher mortality. The pathogenesis of myocardial dysfunction is related to micro and macro circulatory changes, inflammatory response, oxidative stress, intracellular calcium management disturbances, metabolic changes, autonomic dysfunction, activation of apoptosis, mitochondrial abnormalities and a derangement in catecholaminergic stimulation. Since there is no specific treatment for myocardial dysfunction, its management requires an adequate multi systemic support to maintain perfusion pressures and systemic flows sufficient for the regional and global demands.