Left ventricular assist device as a bridge to recovery in a young woman admitted with peripartum cardiomyopathy

Left ventricular assist devices (LVAD) are an effective therapeutic option for end-stage heart failure patients as a bridge to cardiac transplantation in those who deteriorate despite maximal therapy and when a donor heart is not ready available. In some patients, cardiac recovery has been reported while supported by an LVAD. In this case report, we describe a 29-year-old female who was admitted to our centre because of peripartum cardiomyopathy (PPCM). Despite intensive treatment with intravenous inotropes and intra-aortic balloon counter-pulsation she had a persisting low cardiac index and an LVAD was implanted. In the months following implantation the left ventricular systolic function improved and the left ventricular dimensions normalised. Eventually the LVAD could be ex-planted nine months after implantation. At this moment, three years after explantation, echo-cardiography shows a normal-sized left ventricle and almost completely recovered systolic function. (Neth Heart J 2008;16:426-8).     

Insertion of the Impella 5.0 left ventricular assist device via right anterior mini-thoracotomy: a novel practical approach

The Impella 5.0 microaxial pump is a miniaturized left ventricular assist device commonly used for circulatory support in acute cardiogenic shock. The catheter-based pump is designed to be inserted either into a peripheral artery or directly into the ascending aorta. We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.     

The influence of right ventricular stimulation on acute response to cardiac resynchronisation therapy

Background

The contribution of right ventricular (RV) stimulation to cardiac resynchronisation therapy (CRT) remains controversial. RV stimulation might be associated with adverse haemodynamic effects, dependent on intrinsic right bundle branch conduction, presence of scar, RV function and other factors which may partly explain non-response to CRT. This study investigates to what degree RV stimulation modulates response to biventricular (BiV) stimulation in CRT candidates and which baseline factors, assessed by cardiac magnetic resonance imaging, determine this modulation.

Methods and results

Forty-one patients (24 (59 %) males, 67 ± 10 years, QRS 153 ± 22 ms, 21 (51 %) ischaemic cardiomyopathy, left ventricular (LV) ejection fraction 25 ± 7 %), who successfully underwent temporary stimulation with pacing leads in the RV apex (RV_apex) and left ventricular posterolateral (PL) wall were included. Stroke work, assessed by a conductance catheter, was used to assess acute haemodynamic response during baseline conditions and RV_apex, PL (LV) and PL+RV_apex (BiV) stimulation.Compared with baseline, stroke work improved similarly during LV and BiV stimulation (∆+ 51 ± 42 % and ∆+ 48 ± 47 %, both p < 0.001), but individual response showed substantial differences between LV and BiV stimulation. Multivariate analysis revealed that RV ejection fraction (β = 1.01, p = 0.02) was an independent predictor for stroke work response during LV stimulation, but not for BiV stimulation. Other parameters, including atrioventricular delay and scar presence and localisation, did not predict stroke work response in CRT.

Conclusion

The haemodynamic effect of addition of RV_apex stimulation to LV stimulation differs widely among patients receiving CRT. Poor RV function is associated with poor response to LV but not BiV stimulation.

Electronic supplementary material

The online version of this article (doi:10.1007/s12471-015-0770-x) contains supplementary material, which is available to authorized users.     

Delayed expression of cytokines after reperfused myocardial infarction: possible trigger for cardiac dysfunction and ventricular remodeling

Previous studies have shown that 1 wk after permanent coronary artery ligation in rats, some cellular mechanisms involving TNF-alpha occur and contribute to the development of cardiac dysfunction and subsequent heart failure. The aim of the present study was to determine whether similar phenomena also occur after ischemia-reperfusion and whether cytokines other than TNF-alpha can also be involved. Anesthetized male Wistar rats were subjected to 1 h coronary occlusion followed by reperfusion. Cardiac geometry and function were assessed by echocardiography at days 5, 7, 8, and 10 postligation. Before death, heart function was assessed in vivo under basal conditions, as well as after volume overload. Finally, hearts were frozen for histoenzymologic assessment of infarct size and remodeling. The profile of cardiac cytokines was determined by ELISA and ChemiArray on heart tissue extracts. As expected, ischemia-reperfusion induced a progressive remodeling of the heart, characterized by left ventricular free-wall thinning and cavity dilation. Heart function was also decreased in ischemic rats during the first week after surgery. Interestingly, a transient and marked increase in TNF-alpha, IL-1beta, IL-6, cytokine-induced neutrophil chemoattractant (CINC) 2, CINC3, and macrophage inflammatory protein-3alpha was also observed in the myocardium of myocardial ischemia (MI) animals at day 8, whereas the expression of anti-inflammatory interleukins IL-4 and IL-10 remained unchanged. These results suggest that overexpression of proinflammatory cytokines occurring during the first week after ischemia-reperfusion may play a role in the adaptative process in the myocardium and contribute to early dysfunction and remodeling.     

Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells

Most adenoviruses bind to the coxsackie- and adenovirus receptor (CAR). Surprisingly, CAR is not expressed apically on polarized cells and is thus not easily available to viruses. Consequently, alternative mechanisms for entry of coxsackievirus and adenovirus into cells have been suggested. We have found that tear fluid promotes adenovirus infection, and we have identified human lactoferrin (HLf) as the tear fluid component responsible for this effect. HLf alone was found to promote binding of adenovirus to epithelial cells in a dose-dependent manner and also infection of epithelial cells by adenovirus. HLf was also found to promote gene delivery from an adenovirus-based vector. The mechanism takes place at the binding stage and functions independently of CAR. Thus, we have identified a novel binding mechanism whereby adenovirus hijacks HLf, a component of the innate immune system, and uses it as a bridge for attachment to host cells.     

Effect of right ventricular hypertrophy on cardiac performance and the relation between right ventricular systolic peak pressure and end-systolic volume

To investigate the role of hypertrophy of the right ventricle upon right heart performance and the significance of the peak systolic pressure/end-systolic volume (P/V) ratio in terms of right ventricular systolic performance, simultaneous measurements of radionuclide ventriculograms and central hemodynamics were done in 32 patients with chronic obstructive pulmonary disease. In 26 of the patients (80%) technically adequate two-dimensional echocardiograms could be performed. In the subset of patients with increased (greater than or equal to 6 mm) right ventricular end-diastolic wall thickness no relationship between pulmonary artery pressure and right ventricular ejection fraction (RVEF) existed in comparison with the remaining patients. P/V indices and cardiac output were not decreased. Considering the patients, whose P/V ratio did not increase from rest to exercise, RVEF decreased highly significantly more than in the remaining patients. The ratio of wall thickness and end-diastolic radius as determinant of peak systolic stress was significantly decreased in these patients compared with the remaining patients. In the patients with right ventricular hypertrophy despite significantly higher values of pulmonary artery pressures and resistances, the afterload in terms of systolic wall stress is markedly reduced. We conclude that in the hypertrophic state, right ventricular performance is not impaired despite decreased RVEF values. In the patients whose P/V ratio does not increase from rest to exercise, an inappropriate high peak systolic wall stress may exist both due to inadequate wall thickness and increased diameter of the right ventricle. The role of P/V in terms of prognosis and development of decompensated right heart failure remains undetermined.     

Intracellular calcium mishandling leads to cardiac dysfunction and ventricular arrhythmias in a mouse model of propionic acidemia

Propionic acidemia (PA) is a rare metabolic disease associated with mutations in genes encoding the α and β subunits of the enzyme propionyl-CoA carboxylase. The accumulation of toxic metabolites results in mitochondrial dysfunction, increased reactive oxygen species production and oxidative damage, which have been associated with the disease pathophysiology. Clinical symptoms are heterogeneous and include cardiac complications, mainly cardiac dysfunction and arrhythmias, which are recognized as one of the major life-threatening manifestations in patients. We aimed to investigate the molecular mechanisms underlying the cardiac phenotype using a hypomorphic mouse model (Pcca^−/−(A138T)) that recapitulates some biochemical and clinical characteristics of PA. We demonstrate that Pcca^−/−(A138T) mice present with depressed cardiac function along with impaired cell contractility when compared to the wild-type mice. Cardiac dysfunction in Pcca^−/−(A138T) mice was associated with lower systolic Ca²⁺ release ([Ca²⁺]_i transients), impairment in the sarcoplasmic reticulum (SR) Ca²⁺ load and decreased Ca²⁺ re-uptake by SR-Ca²⁺ ATPase (SERCA2a). These functional changes correlated well with the depressed activity of SERCA2a, the elevated ROS levels and SERCA2a oxidation rate in cardiomyocytes isolated from Pcca^−/−(A138T) mice. In addition, decreased SR-Ca²⁺ load in Pcca^−/−(A138T) cardiomyocytes was associated with increased diastolic Ca²⁺ release. The increase in Ca²⁺ sparks, Ca²⁺ waves and spontaneous [Ca²⁺]_i transients in Pcca^−/−(A138T) cardiomyocytes could be responsible for the induction of ventricular arrhythmias detected in these mice. Overall, our results uncover the role of impaired Ca²⁺ handling in arrhythmias and cardiac dysfunction in PA, and identify new targets for the development of therapeutic approaches for this devastating metabolic disease.     

Evaluation of sepsis induced cardiac dysfunction as a predictor of mortality

Background

Sepsis is characterized by life threatening organ dysfunction with dysregulated immune response. Cardiac dysfunction seen in sepsis is unique as it is reversible within 7–10?days. Initial study by Parker et al. in 1984, showed, paradoxically lower ejection fraction in survivors of septic shock. Subsequent meta-analysis did not support that survivors had lower ejection fraction. Aim of our study was to assess the sepsis induced cardiac dysfunction by 2D echocardiography and Troponin I.

Methods

After obtaining institutional ethical committee approval (ref 125/2016), a prospective observational study was done in an university medical college from February 2016 to April 2016. Inclusion criteria were patients diagnosed with sepsis by new sepsis definition. Pregnant patients and patients with poor echo window were excluded. Echocardiographic assessment was done within 48?h of diagnosis of sepsis by standard methods. Primary outcome was ICU mortality and secondary outcome was ICU length of stay. Statistical analysis was done using STATA? (Version14, College station TX).

Results

Fifty eight patients were screened, ten were excluded due to poor echo window. Baseline characteristics were similar in survivors and non survivors, except APACHE II, SOFA age and cumulative fluid balance. Echocardiographic parameters, mitral annular plane systolic excursion (MAPSE), E/e’ and LV systolic function assessed by visual gestalt method were found to be statistically significant. Parameters found significant in bivariate analysis were used as a covariate in logistic regression. APACHE II and MAPSE were significant co-variates in logistic regression with ROC (0.95) and calibration was satisfactory (chi2(df8),1.98, p?=?0.98).

Conclusions

Sepsis induced cardiac dysfunction assessed by echocardiography showed measurement of MAPSE when combined with APACHE II was a good predictor of mortality. Among the echocardiographic parameters MAPSE alone was a good predictor of mortality. Results of this study need further validation from larger study.

     

Inhibition of NF-{kappa}B improves left ventricular remodeling and cardiac dysfunction after myocardial infarction

Several studies have demonstrated that NF-kappaB is substantially involved in the progression of cardiac remodeling; however, it remains uncertain whether the continuous inhibition of NF-kappaB is effective for the prevention of myocardial remodeling. Myocardial infarction (MI) was produced by ligation of the left anterior coronary artery of rats. IMD-0354 (10 mg/kg per day), a novel phosphorylation inhibitor of IkappaB that acts via inhibition of IKK-beta, was injected intraperitoneally starting 24 h after induction of MI for 28 days. After 28 days, the IMD-0354-treated group showed significantly improved survival rate compared with that of the vehicle-treated group (P < 0.05). Although infarct size was similar in both groups, improved left ventricular (LV) remodeling and diastolic dysfunction, as indicated by smaller LV cavity (LV end-diastolic area: vehicle, 74.13 +/- 3.57 mm(2); IMD-0354, 55.00 +/- 3.73 mm(2); P < 0.05), smaller peak velocity of early-to-late filling wave (E/A) ratio (vehicle, 3.87 +/- 0.26; IMD-0354, 2.61 +/- 0.24; P < 0.05), and lower plasma brain natriuretic peptide level (vehicle, 167.63 +/- 14.87 pg/ml; IMD-0354, 110.75 +/- 6.41 pg/ml; P < 0.05), were observed in the IMD-0354-treated group. Moreover, fibrosis, accumulation of macrophages, and expression of several factors (transforming growth factor-beta1, monocyte chemoattractant protein-1, matrix metalloproteinase-9 and -2) in the noninfarcted myocardium was remarkably inhibited by IMD-0354. In conclusion, inhibition of NF-kappaB activation may reduce the proinflammatory reactions and modulate the extracellular matrix and provide an effective approach to prevent adverse cardiac remodeling after MI.     

TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload

TNF-alpha has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-alpha production in myocardial injury due to intracellular Ca2+-overload is available in the literature. The intracellular Ca2+-overload was induced in the isolated rat hearts subjected to 5 min Ca2+-depletion and 30 min Ca2+-repletion (Ca2+-paradox). The Ca2+-paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-alpha content. The ratio of cytosolic to homogenate nuclear factor-kappaB (NFkappaB) was decreased whereas the ratio of phospho-NFkappaB to total NFkappaB was increased in the Ca2+-paradox hearts. All these changes due to Ca2+-paradox were significantly attenuated upon treating the hearts with 100 microM pentoxifylline. These results suggest that activation of NFkappaB and increased production of TNF-alpha may play an important role in cardiac injury due to intracellular Ca2+-overload.     

Cardiac lymphatic interruption is a major cause for allograft failure after cardiac transplantation

Cardiac transplantation is one of the most effective treatments of end stage heart failure to date, although it comes with risks. One of the major complications of cardiac transplantation is allograft failure, which is caused by ischemic injuries, pulmonary hypertension and chronic rejection. Recent animal and human studies have demonstrated that cardiac lymphatic obstruction leads to significant myocardial fibrosis and depression in contractile forces. We hypothesize that lymphatic interruption, which is almost inevitable after cardiac transplantation, is a major cause of cardiac allograft failure through direct damages to the myocardium and also through the formation of allograft coronary vasculopathy.     

Recording of the recovery of fluorescence after bleaching as a method for cell research

The main principles, experimental base and practical application of the method of fluorescence recovery after photobleaching registration are reviewed. The method allows to measure dynamics of the membrane components, to determine diffusion and convection constants, the cell fluorophor mobility etc.     

Heart rate recovery after exercise: a predictor of ventricular fibrillation susceptibility after myocardial infarction

Heart rate recovery after exercise, thought to be related to cardiac parasympathetic tone, has been shown to be a prognostic tool for all-cause mortality. However, the relationship between this variable and confirmed susceptibility to ventricular fibrillation (VF) has not been established. Therefore, myocardial ischemia was induced with a 2-min occlusion of the left circumflex artery during the last minute of exercise in mongrel dogs with myocardial infarction (n = 105 dogs). VF was induced in 66 animals (susceptible), whereas the remaining 39 dogs had no arrhythmias (resistant). On a previous day, ECG was recorded and a time-series analysis of heart rate variability was measured 30, 60, and 120 s after submaximal exercise (treadmill running). The heart rate recovery was significantly greater in resistant dogs than in susceptible dogs at all three times, with the most dramatic difference at the 30-s mark (change from maximum: 48.1 +/- 3.6 beats/min, resistant dogs; 31.0 +/- 2.2 beats/min, susceptible dogs). Correspondingly, indexes of parasympathetic tone increased to a significantly greater extent in resistant dogs at 30 and 60 s after exercise. These differences were eliminated by atropine pretreatment. When considered together, these data suggest that resistant animals exhibit a more rapid recovery of vagal activity after exercise than those susceptible to VF. As such, postexercise heart rate recovery may help identify patients with a high risk for VF following myocardial infarction.     

The formation of the right and left heart ventricles from the ventricular part of the cardiac tube during embryogenesis

It has been generally assumed that the initial rudiment of the heart ventricle is divided by the longitudinal interventricular septum into the right and left ventricles. This paper presents evidence for the hypothesis that the right and the left ventricles are produced during normal development from different sequentially located segments of the cardiac tube. These segments yielding rudiments of the right and left ventricles could be detected even during early embryogenesis. This hypothesis requires a new explanation for the process of the formation of two separate outlets from the heart ventricles.     

Plasma myostatin levels are related to the extent of right ventricular dysfunction in exacerbation of chronic obstructive pulmonary disease

Objective: To investigate the relationship between plasma myostatin levels and right ventricle (RV) dysfunction (RVD) in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

Methods: The study recruited 84 patients with AECOPD. Plasma myostatin was analyzed and tricuspid annular plane systolic excursion (TAPSE)?<?16?mm was used as the main indicator for RVD.

Results: Plasma myostatin levels were significantly higher in 47 patients with RVD than 37 ones without (P?<?0.005). Multivariate regression analysis revealed that myostatin levels correlated significantly with TAPSE values and RV myocardial performance index (p?<?0.001) among the study patients.

Conclusion: Plasma myostatin is a potential biomarker for improving diagnosis of RVD in AECOPD.