Stroke risk associated with balloon based catheter ablation for atrial fibrillation: Rationale and design of the MACPAF Study

<p>Abstract</p> <p>Background</p> <p>Catheter ablation of the pulmonary veins has become accepted as a standard therapeutic approach for symptomatic paroxysmal atrial fibrillation (AF). However, there is some evidence for an ablation associated (silent) stroke risk, lowering the hope to limit the stroke risk by restoration of rhythm over rate control in AF. The purpose of the prospective randomized single-center study "Mesh Ablator versus Cryoballoon Pulmonary Vein Ablation of Symptomatic Paroxysmal Atrial Fibrillation" (MACPAF) is to compare the efficacy and safety of two balloon based pulmonary vein ablation systems in patients with symptomatic paroxysmal AF.</p> <p>Methods/Design</p> <p>Patients are randomized 1:1 for the Arctic Front^®or the HD Mesh Ablator^®catheter for left atrial catheter ablation (LACA). The predefined endpoints will be assessed by brain magnetic resonance imaging (MRI), neuro(psycho)logical tests and a subcutaneously implanted reveal recorder for AF detection. According to statistics 108 patients will be enrolled.</p> <p>Discussion</p> <p>Findings from the MACPAF trial will help to balance the benefits and risks of LACA for symptomatic paroxysmal AF. Using serial brain MRIs might help to identify patients at risk for LACA-associated cerebral thromboembolism. Potential limitations of the study are the single-center design, the existence of a variety of LACA-catheters, the missing placebo-group and the impossibility to assess the primary endpoint in a blinded fashion.</p> <p>Trial registration</p> <p>clinicaltrials.gov NCT01061931</p

Cell-to-cell variability in troponin I phosphorylation in a porcine model of pacing-induced heart failure

We tested the hypothesis that myocardial contractile protein phosphorylation and the Ca2+ sensitivity of force production are dysregulated in a porcine model of pacing-induced heart failure (HF). The level of protein kinase A (PKA)-dependent cardiac troponin I (TnI) phosphorylation was lower in the myocardium surrounding the pacing electrode (pacing site) of the failing left ventricle (LV) than in the controls. Immunohistochemical assays of the LV pacing site pointed to isolated clusters of cardiomyocytes exhibiting a reduced level of phosphorylated TnI. Flow cytometry on isolated and permeabilized cardiomyocytes revealed a significantly larger cell-to-cell variation in the level of TnI phosphorylation of the LV pacing site than in the opposite region in HF or in either region in the controls: the interquartile range (IQR) on the distribution histogram of relative TnI phosphorylation was wider at the pacing site (IQR = 0.53) than that at the remote site of HF (IQR = 0.42; P = 0.0047) or that of the free wall of the control animals (IQR = 0.36; P = 0.0093). Additionally, the Ca2+ sensitivities of isometric force production were higher and appeared to be more variable in single permeabilized cardiomyocytes from the HF pacing site than in the healthy myocardium. In conclusion, the level of PKA-dependent TnI phosphorylation and the Ca2+ sensitivity of force production exhibited a high cell-to-cell variability at the LV pacing site, possibly explaining the abnormalities of the regional myocardial contractile function in a porcine model of pacing-induced HF

The “Missing” Link Between Acute Hemodynamic Effect and Clinical Response

The hemodynamic, mechanical and electrical effects of cardiac resynchronization therapy (CRT) occur immediate and are lasting as long as CRT is delivered. Therefore, it is reasonable to assume that acute hemodynamic effects should predict long-term outcome. However, in the literature there is more evidence against than in favour of this idea. This raises the question of what factor(s) do relate to the benefit of CRT. There is increasing evidence that dyssynchrony, presumably through the resultant abnormal local mechanical behaviour, induces extensive remodelling, comprising structure, as well as electrophysiological and contractile processes. Resynchronization has been shown to reverse these processes, even in cases of limited hemodynamic improvement. These data may indicate the need for a paradigm shift in order to achieve maximal long-term CRT response

Animal Models of Dyssynchrony

Cardiac resynchronization therapy (CRT) is an important therapy for patients with heart failure and conduction pathology, but the benefits are heterogeneous between patients and approximately a third of patients do not show signs of clinical or echocardiographic response. This calls for a better understanding of the underlying conduction disease and resynchronization. In this review, we discuss to what extent established and novel animal models can help to better understand the pathophysiology of dyssynchrony and the benefits of CRT

Electrical and Mechanical Ventricular Activation During Left Bundle Branch Block and Resynchronization

Cardiac resynchronization therapy (CRT) aims to treat selected heart failure patients suffering from conduction abnormalities with left bundle branch block (LBBB) as the culprit disease. LBBB remained largely underinvestigated until it became apparent that the amount of response to CRT was heterogeneous and that the therapy and underlying pathology were thus incompletely understood. In this review, current knowledge concerning activation in LBBB and during biventricular pacing will be explored and applied to current CRT practice, highlighting novel ways to better measure and treat the electrical substrate

Rapid automatic segmentation of abnormal tissue in late gadolinium enhancement cardiovascular magnetic resonance images for improved management of long-standing persistent atrial fibrillation

Background: Atrial fibrillation (AF) is the most common heart rhythm disorder. In order for late Gd enhancement cardiovascular magnetic resonance (LGE CMR) to ameliorate the AF management, the ready availability of the accurate enhancement segmentation is required. However, the computer-aided segmentation of enhancement in LGE CMR of AF is still an open question. Additionally, the number of centres that have reported successful application of LGE CMR to guide clinical AF strategies remains low, while the debate on LGE CMR’s diagnostic ability for AF still holds. The aim of this study is to propose a method that reliably distinguishes enhanced (abnormal) from non-enhanced (healthy) tissue within the left atrial wall of (pre-ablation and 3 months post-ablation) LGE CMR data-sets from long-standing persistent AF patients studied at our centre. Methods: Enhancement segmentation was achieved by employing thresholds benchmarked against the statistics of the whole left atrial blood-pool (LABP). The test-set cross-validation mechanism was applied to determine the input feature representation and algorithm that best predict enhancement threshold levels. Results: Global normalized intensity threshold levels T PRE = 1 1/4 and T POST = 1 5/8 were found to segment enhancement in data-sets acquired pre-ablation and at 3 months post-ablation, respectively. The segmentation results were corroborated by using visual inspection of LGE CMR brightness levels and one endocardial bipolar voltage map. The measured extent of pre-ablation fibrosis fell within the normal range for the specific arrhythmia phenotype. 3D volume renderings of segmented post-ablation enhancement emulated the expected ablation lesion patterns. By comparing our technique with other related approaches that proposed different threshold levels (although they also relied on reference regions from within the LABP) for segmenting enhancement in LGE CMR data-sets of AF patients, we illustrated that the cut-off levels employed by other centres may not be usable for clinical studies performed in our centre. Conclusions: The proposed technique has great potential for successful employment in the AF management within our centre. It provides a highly desirable validation of the LGE CMR technique for AF studies. Inter-centre differences in the CMR acquisition protocol and image analysis strategy inevitably impede the selection of a universally optimal algorithm for segmentation of enhancement in AF studies

2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation: executive summary.

S