Connexin 43 expression in human hypertrophied heart due to pressure and volume overload

Left ventricular hypertrophy (LVH) is due to pressure overload or mechanical stretch and is thought to be associated with remodeling of gap-junctions. We investigated whether the expression of connexin 43 (Cx43) is altered in humans in response to different degrees of LVH. The expression of Cx43 was analyzed by quantitative polymerase chain reaction, Western blot analysis and immunohistochemistry on left ventricular biopsies from patients undergoing aortic or mitral valve replacement. Three groups were analyzed: patients with aortic stenosis with severe LVH (n=9) versus only mild LVH (n=7), and patients with LVH caused by mitral regurgitation (n=5). Cx43 mRNA expression and protein expression were similar in the three groups studied. Furthermore, immunohistochemistry revealed no change in Cx43 distribution. We can conclude that when compared with mild LVH or with LVH due to volume overload, severe LVH due to chronic pressure overload is not accompanied by detectable changes of Cx43 expression or spatial distribution.

Right ventricular systolic function and cardiac resynchronization therapy

AIMS: The effect of cardiac resynchronization therapy (CRT) on right ventricular ejection fraction (RVEF) has not been well studied. Furthermore, it is unclear whether baseline RVEF influences response to CRT. To evaluate the acute and chronic effects of CRT on right ventricular systolic function, and to investigate whether baseline RVEF impacts response to CRT. METHODS AND RESULTS: Forty-four patients with a standard indication for CRT underwent radionuclide angiography at baseline and after at least 6 months' follow-up for measuring RVEF, right ventricular synchrony (using phase analysis), and left ventricular ejection fraction (LVEF). In addition, NYHA functional class and 6-min walking distance (6MWD) were evaluated. There were no significant acute changes in RVEF with CRT. After a mean follow-up of 9 +/- 5 months, RVEF was slightly improved (by 1.9 +/- 5.0% in absolute terms, P = 0.016), and to a lesser extent than LVEF (5.1 +/- 9.0%, P = 0.009 compared with RVEF). Right ventricular dyssynchrony was significantly improved at follow-up (P = 0.016). Patients with a baseline RVEF < or = 0.35 (n = 19) were less likely to improve in NYHA class (P = 0.016), and also tended to improve less in 6MWD and LVEF (P < 0.06). CONCLUSION: Cardiac resynchronization therapy has no acute effect on RVEF, and only slightly improves RVEF at follow-up. Patients with reduced RVEF at baseline were less likely to respond to CRT, indicating that right ventricular systolic dysfunction may play a role in patient selection.

Ventricular prosthesis embolization during transapical aortic valve implantation: the role of transesophageal echocardiography in diagnosis and management

The authors present the case of an 81-year-old patient with severe aortic stenosis who experienced left ventricular embolization of an aortic bioprosthesis during transapical aortic valve implantation. The authors discuss reasons for prosthesis embolization and reinforce the attention to technical details and the widespread use of multimodality imaging techniques. In this context, transesophageal echocardiography appears indispensable in the detection and management of procedure-related complications.

Ideal site for ventricular anchoring of artificial chordae in mitral regurgitation

Surgical treatment of mitral leaflet prolapse using artificial neochordae shows excellent outcomes. Upcoming devices attempt the same treatment in a minimally invasive way but target the left ventricular apex as an anchoring point, rather than the tip of the corresponding papillary muscle. In this study, cine cardiac magnetic resonance imaging was used to compare these 2 different anchoring positions and their dynamic relationship with the mitral leaflets.

Proteome analysis in cardiovascular pathophysiology using Dahl rat model

Dahl salt-sensitive (DS) and salt-resistant (DR) inbred rat strains represent a well established animal model for cardiovascular research. Upon prolonged administration of high-salt-containing diet, DS rats develop systemic hypertension, and as a consequence they develop left ventricular hypertrophy, followed by heart failure. The aim of this work was to explore whether this animal model is suitable to identify biomarkers that characterize defined stages of cardiac pathophysiological conditions. The work had to be performed in two stages: in the first part proteomic differences that are attributable to the two separate rat lines (DS and DR) had to be established, and in the second part the process of development of heart failure due to feeding the rats with high-salt-containing diet has to be monitored. This work describes the results of the first stage, with the outcome of protein expression profiles of left ventricular tissues of DS and DR rats kept under low salt diet. Substantial extent of quantitative and qualitative expression differences between both strains of Dahl rats in heart tissue was detected. Using Principal Component Analysis, Linear Discriminant Analysis and other statistical means we have established sets of differentially expressed proteins, candidates for further molecular analysis of the heart failure mechanisms.

In Vitro Evaluation of Ventricular Cannulation for Rotodynamic Cardiac Assist Devices

The influence of positioning and geometry of ventricular cannulas for contemporary continuous flow Left Ventricular Assist Devices (LVADs) was evaluated in a non-beating isolated heart preparation with borescopic visualization. Preload and LVAD flow were varied to evaluate degrees of ventricular decompression up to the point of ventricular collapse. The performance of a flanged cannula was compared to a conventional bevel-tipped cannula: quantitatively by the maximal flow attainable, and qualitatively by visualization of fluid tracer particles within the ventricular chamber. Three forms of ventricular suck-down occurred: concentric collapse, gradual entrainment and instantaneous entrainment. In some circumstances, unstable oscillations of the ventricle were observed prior to complete collapse. Under conditions of low preload, the flanged cannula demonstrated less positional sensitivity, provided greater flow, and exhibited fewer areas of stagnation than the beveled cannula. These observations warrant further consideration of a flanged ventricular cannula to mitigate complications encountered with conventional cannulae.

Gender differences of atrial and ventricular remodeling and autonomic tone in nonelite athletes

Veteran endurance athletes have an increased risk of developing atrial fibrillation (AF), with a striking male predominance. We hypothesized that male athletes were more prone to atrial and ventricular remodeling and investigated the signal-averaged P wave and factors that promote the occurrence of AF. Nonelite athletes scheduled to participate in the 2010 Grand Prix of Bern, a 10-mile race, were invited. Of the 873 marathon and nonmarathon runners who were willing to participate, 68 female and 70 male athletes were randomly selected. The runners with cardiovascular disease or elevated blood pressure (>140/90 mm Hg) were excluded. Thus, 121 athletes were entered into the final analysis. Their mean age was 42 ± 7 years. No gender differences were found for age, lifetime training hours, or race time. The male athletes had a significantly longer signal-averaged P-wave duration (136 ± 12 vs 122 ± 10 ms; p <0.001). The left atrial volume was larger in the male athletes (56 ± 13 vs 49 ± 10 ml; p = 0.001), while left atrial volume index showed no differences (29 ± 7 vs 30 ± 6 ml/m²; p = 0.332). In male athletes, the left ventricular mass index (107 ± 17 vs 86 ± 16 g/m²; p <0.001) and relative wall thickness (0.44 ± 0.06 vs 0.41 ± 0.07; p = 0.004) were greater. No differences were found in the left ventricular ejection fraction (63 ± 4% vs 66 ± 6%; p = 0.112) and mitral annular tissue Doppler e' velocity (10.9 ± 1.5 vs 10.6 ± 1.5 cm/s; p = 0.187). However, the tissue Doppler a' velocity was higher (8.7 ± 1.2 vs 7.6 ± 1.3 cm/s; p < 0.001) in the male athletes. Male athletes had a higher systolic blood pressure at rest (123 ± 9 vs 110 ± 11 mm Hg; p < 0.001) and at peak exercise (180 ± 15 vs 169 ± 19 mm Hg; p = 0.001). In the frequency domain analysis of heart rate variability, the sympatho-vagal balance, represented by the low/high-frequency power ratio, was significantly greater in male athletes (5.8 ± 2.8 vs 3.9 ± 1.9; p < 0.001). Four athletes (3.3%) had at least one documented episode of paroxysmal AF, all were men (p = 0.042). In conclusion, for a comparable amount of training and performance, male athletes showed a more pronounced atrial remodeling, a concentric type of ventricular remodeling, and an altered diastolic function. A higher blood pressure at rest and during exercise and a higher sympathetic tone might be causal. The altered left atrial substrate might facilitate the occurrence of AF.

Impact of salt on cardiac differential gene expression and coronary lesion in normotensive mineralocorticoid-treated mice

We previously reported that excess of deoxycorticosterone-acetate (DOCA)/salt-induced cardiac hypertrophy in the absence of hypertension in one-renin gene mice. This model allows us to study molecular mechanisms of high-salt intake in the development of cardiovascular remodeling, independently of blood pressure in a high mineralocorticoid state. In this study, we compared the effect of 5-wk low- and high-salt intake on cardiovascular remodeling and cardiac differential gene expression in mice receiving the same amount of DOCA. Differential gene and protein expression was measured by high-density cDNA microarray assays, real-time PCR and Western blot analysis in DOCA-high salt (HS) vs. DOCA-low salt (LS) mice. DOCA-HS mice developed cardiac hypertrophy, coronary perivascular fibrosis, and left ventricular dysfunction. Differential gene and protein expression demonstrated that high-salt intake upregulated a subset of genes encoding for proteins involved in inflammation and extracellular matrix remodeling (e.g., Col3a1, Col1a2, Hmox1, and Lcn2). A major subset of downregulated genes encoded for transcription factors, including myeloid differentiation primary response (MyD) genes. Our data provide some evidence that vascular remodeling, fibrosis, and inflammation are important consequences of a high-salt intake in DOCA mice. Our study suggests that among the different pathogenic factors of cardiac and vascular remodeling, such as hypertension and mineralocorticoid excess and sodium intake, the latter is critical for the development of the profibrotic and proinflammatory phenotype observed in the heart of normotensive DOCA-treated mice.

Control of ventricular unloading using an electrocardiogram-synchronized Thoratec paracorporeal ventricular assist device

OBJECTIVE: Current pulsatile ventricular assist devices operate asynchronous with the left ventricle in fixed-rate or fill-to-empty modes because electrocardiogram-triggered modes have been abandoned. We hypothesize that varying the ejection delay in the synchronized mode yields more precise control of hemodynamics and left ventricular loading. This allows for a refined management that may be clinically beneficial. METHODS: Eight sheep received a Thoratec paracorporeal ventricular assist device (Thoratec Corp, Pleasanton, Calif) via ventriculo-aortic cannulation. Left ventricular pressure and volume, aortic pressure, pulmonary flow, pump chamber pressure, and pump inflow and outflow were recorded. The pump was driven by a clinical pneumatic drive unit (Medos Medizintechnik AG, Stolberg, Germany) synchronously with the native R-wave. The start of pump ejection was delayed between 0% and 100% of the cardiac period in 10% increments. For each of these delays, hemodynamic variables were compared with baseline data using paired t tests. RESULTS: The location of the minimum of stroke work was observed at a delay of 10% (soon after aortic valve opening), resulting in a median of 43% reduction in stroke work compared with baseline. Maximum stroke work occurred at a median delay of 70% with a median stroke work increase of 11% above baseline. Left ventricular volume unloading expressed by end-diastolic volume was most pronounced for copulsation (delay 0%). CONCLUSIONS: The timing of pump ejection in synchronized mode yields control over left ventricular energetics and can be a method to achieve gradual reloading of a recoverable left ventricle. The traditionally suggested counterpulsation is not optimal in ventriculo-aortic cannulation when maximum unloading is desired.

In vitro hemodynamic evaluation of ventricular suction conditions of the EVAHEART ventricular assist pump

Purpose: Mismatches between pump output and venous return in a continuous-flow ventricular assist device may elicit episodes of ventricular suction. This research describes a series of in vitro experiments to characterize the operating conditions under which the EVAHEART centrifugal blood pump (Sun Medical Technology Research Corp., Nagano, Japan) can be operated with minimal concern regarding left ventricular (LV) suction. Methods: The pump was interposed into a pneumatically driven pulsatile mock circulatory system (MCS) in the ventricular apex to aorta configuration. Under varying conditions of preload, afterload, and systolic pressure, the speed of the pump was increased step-wise until suction was observed. Identification of suction was based on pump inlet pressure. Results: In the case of reduced LV systolic pressure, reduced preload (=10 mmHg), and afterload (=60 mmHg), suction was observed for speeds =2,200 rpm. However, suction did not occur at any speed (up to a maximum speed of 2,400 rpm) when preload was kept within 10-14 mmHg and afterload =80 mmHg. Although in vitro experiments cannot replace in vivo models, the results indicated that ventricular suction can be avoided if sufficient preload and afterload are maintained. Conclusion: Conditions of hypovolemia and/or hypotension may increase the risk of suction at the highest speeds, irrespective of the native ventricular systolic pressure. However, in vitro guidelines are not directly transferrable to the clinical situation; therefore, patient-specific evaluation is recommended, which can be aided by ultrasonography at various points in the course of support.

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.

Do women have impaired regional systolic function in hypertensive heart disease? A 3-dimensional echocardiography study

AIMS: In pressure overload left ventricular (LV) hypertrophy, gender-related differences in global LV systolic function have been previously reported. The goal of this study was to determine regional systolic function of the left ventricle in male and female patients with hypertensive heart disease. METHODS AND RESULTS: Regional LV function was analyzed from multiplane transesophageal echocardiography with three-dimensional (3D) reconstruction of the left ventricle. In 24 patients (13 males and 11 females), four parallel (2 basal and 2 apical) equidistant short axis cross-sections from base to apex were obtained from the reconstructed LV. In each short axis 24 wall-thickness measurements were carried out at 15 degrees intervals at end-diastole and end-systole. Thus, a total of 192 measurements were obtained in each patient. Wall thickening was calculated as difference of end-diastolic and end-systolic wall thickness, and fractional thickening as thickening divided by end-diastolic thickness. Fractional thickening and wall stress were inversely related to end-diastolic wall thickness in both, males and females. Females showed less LV systolic function when compared to males (p<0.001). However, when corrected for wall stress, which was higher in females, there was no gender difference in systolic function. CONCLUSION: There are regional differences in LV systolic function in females and males which are directly related to differences in wall stress. Thus, gender-related differences in LV regional function are load-dependent and not due to structural differences.

[Fixed-combination of losartan/hydrochlorothiazide 100 mg/25 mg. Tolerability and efficacy on blood pressure measured in the practice and for 24 hours]

BACKGROUND: A high proportion of patients with essential hypertension need a combination therapy to reach the therapeutic goal. In the present study, the tolerability and efficacy of a fixed, once daily combination of the AT1 blocker Losartan (100 mg) and the diuretic hydrochlorothiazide (HCTZ) (25 mg) for patients in the real-life situation was investigated. Special consideration was given to the results of ambulatory 24-hourblood pressure (ABP) measurements. METHODS: The open label, prospective non-interventional surveillance study took place from October 2005 to June 2006. A total of 1139 patients over 18 years in age were included whose blood pressures could not be adequately treated with HCTZ alone and for whom an individual dose titration for Losartan and HCTZ had already been performed. RESULTS: The average age (+/- standard deviation) of the patients was 61.2 +/- 11.6 years; 55.8% were men. Comorbidities were common. Specifically, left ventricular hypertrophy was present in 3.1% of the patients, coronary heart disease in 30.1%, chronic heart failure in 11.8% and status post myocardial infarction in 10.5%, respectively. In addition to the Losartan/HCTZ treatment, 61.0% of the patients received a second antihypertensive medicine. After an average treatment duration of 50.4 +/- 17.2 days, the base line systolic blood pressure of 160.8 +/- 16.3 mmHg decreased by 24.0 +/- 17.0 mmHg (-14.4%) and the diastolic blood pressure of 94.4 +/- 9.9 mmHg decreased by 11.8 +/- 10.2 mmHg (-11.8%). For the ABP measurements, the overall average systolic and diastolic blood pressures fell by 16.9 +/- 14.2 mmHg and 8.8 +/-10.3 mmHg, the day average by 17.3 +/- 14.8 mmHg and 9.0 +/- 10.2 mmHg and the night average by 15.1 +/- 17.6 mmHg and 7.8 +/- 11.7 mmHg, respectively. In twelve of the 1139 patients (1.1%), a total of 15 adverse events occurred. A causal connection with the medication was suspected in only in one case (one patient with three). CONCLUSION: The combination of Losartan/HCTZ 100/25 mg, as the exclusive therapy or in addition to other antihypertensive medicines, was for patients, many of whom who had comorbidities, in the real-life situation well tolerated and effective. The efficacy was demonstrated also during the night through ABP.

Traumatic free wall and ventricular septal rupture - 'hybrid' management in a child

A 8-year-old boy showed a traumatic ventricular septal rupture following a blunt chest trauma, and was scheduled for elective catheter closure. Two weeks later, a follow-up echocardiogram revealed a pseudoaneurysm of the anterior wall of the left ventricle. Because of the apical location of the VSD, it was decided to proceed with transcatheter occlusion. After successful VSD closure, the patient was taken to the operation room for surgical repair of the left ventricular pseudoaneurysm. Symptoms and signs seen in patients with ventricular pseudoaneurysms appear to be discrete and variable, and a high clinical index of suspicion with a very close echocardiographic follow-up is strongly recommended after occurrence of a blunt cardiac trauma. The combined 'hybrid' approach of transcatheter closure of the intraventricular rupture followed by surgical closure of the pseudoaneurysm allows for a less invasive and efficient management of this rare combination of post-traumatic ventricular free wall and septal rupture in a child.

Percutaneous ventricular assist devices for cardiogenic shock

Cardiogenic shock complicates up to 7% of ST-segment elevation myocardial infarctions and 2.5% of non-ST-segment elevation myocardial infarctions, with an associated mortality of 50% to 70%. Primary cardiac pump failure is followed by secondary vital organ hypoperfusion and subsequent activation of various cascade pathways, resulting in a downward spiral leading to multiple organ failure and, ultimately, death. Immediate restoration of cardiac output by means of percutaneous ventricular assist devices restores hemodynamic -stability and is an important advance in the management of patients with severe left ventricular dysfunction and cardiogenic shock. This article reviews available evidence supporting the use of percutaneous ventricular assist devices in patients suffering from cardiogenic shock.