Morphological and molecular changes of the myocardium after left ventricular mechanical support

Baba, Hideo A.; Wohlschlaeger, Jeremias

doi:10.1016/j.yjmcc.2008.09.593

Cited by 8 publications

(15 citation statements)

References 103 publications

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“…In those cases a pseudo-alternans is created at the border between the m = n and m > n regions, which we refer to here as Gaskell alternans, as he was the first to suggest that mechanical alternans could be the result of a 2:1 sub-region in an otherwise 1:1 domain (Gaskell, 1882). Gaskell-type alternans of APD was first described numerically by Arce et al (2000) and then experimentally by Fenton et al (2008a) in equine atria and later by Myles et al (2008) in rabbit ventricles with myocardial infarction. It is possible that Gaskell alternans is the type of alternans most commonly observed during ischemia.…”

Section: Discussionmentioning

confidence: 96%

“…This behavior can result in very large local gradients of repolarization during consecutive beats that can cause conduction block (Watanabe et al, 2001; Fox et al, 2002) and the initiation of arrhythmias (Choi and Salama, 2000; Cherry and Fenton, 2008) such as tachycardia and fibrillation, as shown in Figure 1B. Although there have been many studies quantifying the dynamics of alternans in space, they have all been conducted in monolayers (Shiferaw et al, 2005; Bien et al, 2006; Jia et al, 2007; Kim et al, 2007; de Diego et al, 2008; Weinberg et al, 2010) or small mammalian hearts (Pastore et al, 1999; Choi and Salama, 2000; Pastore and Rosenbaum, 2000; Walker et al, 2003; Hayashi et al, 2007; Mironov et al, 2008; Myles et al, 2008, 2011; Hsieh et al, 2009; Ziv et al, 2009). …”

Section: Introductionmentioning

confidence: 99%

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Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

Gizzi¹,

Cherry²,

Gilmour³

et al. 2013

Front. Physiol.

112

114

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Alternans of action potential duration has been associated with T wave alternans and the development of arrhythmias because it produces large gradients of repolarization. However, little is known about alternans dynamics in large mammalian hearts. Using optical mapping to record electrical activations simultaneously from the epicardium and endocardium of 9 canine right ventricles, we demonstrate novel arrhythmogenic complex spatiotemporal dynamics. (i) Alternans predominantly develops first on the endocardium. (ii) The postulated simple progression from normal rhythm to concordant to discordant alternans is not always observed; concordant alternans can develop from discordant alternans as the pacing period is decreased. (iii) In contrast to smaller tissue preparations, multiple stationary nodal lines may exist and need not be perpendicular to the pacing site or to each other. (iv) Alternans has fully three-dimensional dynamics and the epicardium and endocardium can show significantly different dynamics: multiple nodal surfaces can be transmural or intramural and can form concave/convex surfaces resulting in islands of discordant alternans. (v) The complex spatiotemporal patterns observed during alternans are very sensitive to both the site of stimulation and the stimulation history. Alternans in canine ventricles not only exhibit larger amplitudes and persist for longer cycle length regimes compared to those found in smaller mammalian hearts, but also show novel dynamics not previously described that enhance dispersion and show high sensitivity to initial conditions. This indicates some underlying predisposition to chaos and can help to guide the design of new drugs and devices controlling and preventing arrhythmic events.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

Gizzi¹,

Cherry²,

Gilmour³

et al. 2013

Front. Physiol.

112

114

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“…Recent studies pointed out the remodeling capacity of cardiomyocytes of chronically failing hearts in response to VAD implantation [17,18]. At a translational level, these studies have compared the pre-and post-VAD cardiomyocytes with regard to functional contractility and gene expression profiling.…”

Section: Discussionmentioning

confidence: 99%

Pathological Findings in Cardiac Apex Removed during Implantation of Left Ventricular Assist Devices (LVAD) are Non-Specific. A 13-Year-Experience at a German Heart Center

Strecker

Agaimy

Roesch

et al. 2015

Thorac cardiovasc Surg

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Background and aim: Ventricular assist devices (VAD) have become an established therapy for patients with end-stage heart failure. The two main reasons for this development are the shortage of appropriate donor organs and the increasing number of patients waiting for heart transplantation (HTX). Furthermore, the enormous advances in the technical equipment and the rising clinical experience have improved the implantation technique, the durability and the long-term patient outcomes. Methods: We reviewed all cases of left ventricular assist device (LVAD) implantation at our Erlangen Heart Center during January 2000-July 2013. The main aim of this study was to analyze the underlying pathology from the cardiac apex removed during the implantation. From all patients, we created a follow-up, analyzed the pathological features with the clinical diagnoses and described the overall outcome. Results: VAD implantation was performed in 266 cases at our center in the last 13 years (2.2% of the total of 12254 cardiac surgical operations in that period). From these patients, 223 underwent LVAD or biventricular (BVAD) implantation; the remaining received a right (RVAD) implantation. The most frequent underlying clinical diagnoses were dilated (n = 84, 37.7%, DCM) or ischemic (n = 61, 27.4%, ICM) cardiomyopathy. The pathological findings in the apex biopsy were generally non-specific and showed variable interstitial myocardial fibrosis with evidence of fibre loss, fatty degeneration and variable irregular atrophy of muscle fibres, consistent with dilated and ischemic cardiomyopathies as the most frequent causes of heart failure in these patients. Only a few cases showed other specific features such as myocarditis and AL-amyloidosis. Conclusions: Pathological findings in cardiac apex removed during LVAD implantation are rather non-specific and they generally reflect the late stage or consequences of chronic myocardial damage in cases of dilated or ischemic cardiomyopathies. Variable patchy chronic inflammatory changes may be observed in cardiomyopathies as a non-specific reaction caused by myocardial fiber damage and should not lead to misinterpretation as evidence of myocarditis or revision of original diagnosis.

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“…Myocardial recovery during VAD support occurs at the different levels with different rates. Whereas at the cellular, molecular, and genomic level there is a high probability of relevant recovery, at the organ level (heart anatomy and function), reverse remodelling and improvement of contractile function detectable by echocardiography are less frequent and, finally, clinically sufficient and stable cardiac recovery which allows VAD explantation occurs in only a few patients , . Patients who were successfully weaned from their VAD often showed only incomplete recovery at the time of VAD explantation, and HF recurred in about a half of the weaned patients during the first 10 years post‐weaning .…”

Section: Unloading‐promoted Reverse Remodelling and Myocardial Recoverymentioning

confidence: 99%

“…Regression of LV dilation during LVAD support consecutive to the reduction of mechanical stretch also facilitates ECM changes, and the restoration of collagen networks in turn can facilitate improvement in ventricular geometry and function , , . Changes in the ECM, which are involved in ventricle dilation during HF development, appeared to be related to up‐regulation of matrix metalloproteinases (MMPs) that cleave matrix components and down‐regulation of their inhibitors (TIMPs) , . LVAD support can reverse this process and thus restore the collagen networks , .…”

Section: Unloading‐promoted Reverse Remodelling and Myocardial Recoverymentioning

confidence: 99%

Contribution of ventricular assist devices to the recovery of failing hearts: a review and the Berlin Heart Center Experience

Dandel

Knosalla

Hetzer

2013

European J of Heart Fail

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Ventricular assist-device (VAD) implantation is a life-saving therapy which will later become either a bridge-to-transplantation or definitive therapy if heart transplantation (HTx) is not possible. VAD-supported failing hearts often recover at the molecular and cellular level, but translation of these changes into functionally stable cardiac recovery allowing long-term HTx/VAD-free outcomes after VAD removal is relatively rare, related to the aetiology, severity, and duration of myocardial damage. The reason for the discrepancy between high recovery rates on cellular and molecular levels and the low rate of cardiac recovery allowing VAD explantation is unknown. For selected patients VAD explantation is feasible. HTx/VAD-free outcomes for >15 years are possible even if recovery remains incomplete and the underlying cause for VAD implantation was idiopathic dilated cardiomyopathy. Echocardiography and right heart catheterization are necessary to assess clinically relevant cardiac recovery. Certain echo parameters appeared highly predictive for post-weaning cardiac function and reliable for weaning decisions. The elective therapeutic use of VADs for heart failure (HF) reversal in its earlier stages is a future goal possibly achievable by development of tools to predict HF reversibility already before VAD implantation and increase the number of weaning candidates by improvement of adjunctive therapies to optimize unloading-promoted recovery. The present article summarizes the knowledge about unloading-promoted myocardial recovery and reviews the available data on its clinical relevance, its post-explant stability, and its assessment for decision-making in favour of or against VAD explantation.

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Morphological and molecular changes of the myocardium after left ventricular mechanical support

Cited by 8 publications

References 103 publications

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

Effects of Pacing Site and Stimulation History on Alternans Dynamics and the Development of Complex Spatiotemporal Patterns in Cardiac Tissue

Pathological Findings in Cardiac Apex Removed during Implantation of Left Ventricular Assist Devices (LVAD) are Non-Specific. A 13-Year-Experience at a German Heart Center

Contribution of ventricular assist devices to the recovery of failing hearts: a review and the Berlin Heart Center Experience

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