Peter Fahmy

Intramyocardial Adiposity After Myocardial Infarction New Implications of a Substrate for Ventricular Tachycardia

Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P⩽0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation ( r ) with conduction velocity ( r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude ( r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups ( P >0.29). However, the MI+VT+ group demonstrated a significant (all P ≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength ( P <0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI. # Clinical Perspective {#article-title-48}

Pre-Disposing and Precipitating Factors in Men With Spontaneous Coronary Artery Dissection

Spontaneous coronary artery dissection (SCAD) is an infrequent but important cause of myocardial infarction (MI) in younger women. The underlying cause, presentation, and natural history of SCAD in women are increasingly being described because >90% of cases affect women. However, SCAD in men is

Human Connexin40 Mutations Slow Conduction and Increase Propensity for Atrial Fibrillation

BACKGROUND Patch clamping studies using non-cardiomyocytes revealed that the human connexin40 mutations P88S, G38D, and A96S are associated with reduced gap junction conductances compared to wild type connexin40 (wtCx40). Their effects within myocytes however are unclear. We aimed to characterise P88S, G38D, and A96S after expression in rat hearts and primary cardiomyocyte cultures. METHODS Adult Sprague-Dawley rat atria were transduced with a lentivector containing a transgene encoding wtCx40, P88S, G38D, A96S, or eGFP (n=6 per transgene). Electrophysiology studies (EPS) were performed just prior to and 7 days after surgery. Left atria were assessed for connexin expression, mRNA levels, inflammation and fibrosis. Primary cardiomyocyte cultures were also transduced with the abovementioned vectors (n=6 per transgene) and monolayer conduction velocities (CV) and protein expression were assessed at 96hours. RESULTS At day 7 EPS, P wave and induced atrial fibrillation (AF) durations were significantly longer in the mutant groups when compared to wtCx40 controls (p<0.05). There were no significant differences in inflammation, fibrosis, or heart to body weight ratios. Monolayer CVs were reduced in the A96S group compared to the wtCx40 group. While similar to wtCx40 controls, P88S velocities were reduced compared to eGFP controls. G38D monolayers possessed spontaneous fibrillatory activity and could not be paced. Immunofluorescence revealed that P88S and G38D reduced native connexin43 myocyte coupling while A96S appeared to co-localise with connexin43 in gap junctions. Connexin43 mRNA levels were similar between groups. CONCLUSIONS The A96S, G38D, and P88S Cx40 mutations slow conduction and increased the propensity for inducible AF.

Retrieval of embolized left atrial appendage devices

Percutaneous left atrial appendage (LAA) closure is gaining interest as an alternative option for prevention of strokes in patients with Atrial Fibrillation (AF), especially for those with contraindications to anticoagulation. Complications from these procedures are well described in the medical literature. LAA closures may lead to pericardial effusion, device‐associated thrombus, and device embolization. Understanding the reasons for embolization, strategies to avoid embolization, and the techniques for retrieval of LAA devices (ACP/AMULET and WATCHMAN) should be appreciated by endovascular implanters. We describe two cases of LAA device embolization that were both successfully retrieved percutaneously and other percutaneous techniques to safely retrieve embolized LAA devices.

ACCURACY OF INTERPRETING FAX TO EMAIL ST-ELEVATION MYOCARDIAL INFARCTION ELECTROCARDIOGRAMS VIEWED ON SMARTPHONES

Timely review and interpretation of 12-lead electrocardiogram (ECG) reduces the time to reperfusion in acute ST-segment elevation myocardial infarction (STEMI). Smartphones are becoming an integral part of a wide variety of medical disciplines, and may be an ideal tool for timely assessment of ECG

Stroke Prevention with Percutaneous Left Atrial Appendage Closure

Atrial fibrillation (AF) is the most common cardiac arrhythmia with increasing prevalence. AF is associated with considerable morbidity and mortality. Cardioembolic stroke results as a consequence of thrombus formation within the left atrial appendage (LAA) in patients with AF and has a significant impact on our health system. Oral anticoagulation with either vitamin K antagonists or the novel anticoagulants is an effective medical therapy for prophylaxis against strokes in patients suffering from AF. Unfortunately, bleeding complications and compliance issues limit their use. A need for newer approaches have thereby been developed and studied such as percutaneous occlusion of the LAA. Several LAA occlusion devices have been developed, and with improved operator experience, they have been successful in stroke prevention in patients with nonvalvular AF and fewer periprocedural complications. This article reviews the use of percutaneous LAA occlusion devices in the prevention of cardioembolic stroke.

TCT-180 Predisposing and Precipitating Factors in Men with Spontaneous Coronary Artery Dissection

revascularization of the culprit lesion in 67,5% of patients (23 PCI, 1ACTP, 1 CABG) with in-hospital death of 8% (3 patients: 2 cases which the dissection progressed retrogradely during PCI and involved the left main and complicated by cardiogenic shock and 1 case involving also the aortic root). 21.6% of cases were initially treated with fibrinolysis which was also significantly related with MACE (p1⁄40.001). PCI was successful in 99.5% of cases. 2 or more stents were needed in 50% of cases and the medium stent length was 46.7 32.4 mm [SD]. During a mean angiographic follow-up of 1023 days the 85% of them didn’t have any images of dissection.

Intramyocardial Adiposity After Myocardial InfarctionClinical Perspective: New Implications of a Substrate for Ventricular Tachycardia

Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P⩽0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation ( r ) with conduction velocity ( r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude ( r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups ( P >0.29). However, the MI+VT+ group demonstrated a significant (all P ≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength ( P <0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI. # Clinical Perspective {#article-title-48}

Intramyocardial Adiposity After Myocardial InfarctionClinical Perspective

Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation (r) with conduction velocity (r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude (r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups (P>0.29). However, the MI+VT+ group demonstrated a significant (all P⩽0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength (P<0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI.Background— Collagen has been attributed as the principal structural substrate of ventricular tachycardia (VT) after myocardial infarction (MI), even though adiposity of myocardium after MI is well recognized histologically. We investigated the effects of intramyocardial adiposity compared with collagen on electrophysiological properties, connexin43 expression, and VT induction after MI. Methods and Results— Simultaneous left ventricular plunge-needle, noncontact mapping was performed in sheep without MI (MI−; n=5), with MI and inducible VT (MI+VT+; n=7), and with MI and no inducible VT (MI+VT−; n=8). Histological intramyocardial quantity of adipose and collagen and degree of discontinuity were coregistered with electrophysiological parameters (MI+; 290 specimens). Additional assessment of connexin43 expression was performed. Left ventricular scar contained a body mass–independent abundance of adipocytes (adipose:collagen=0.8). Increased adipose density and discontinuity contributed to a greater inverse correlation ( r ) with conduction velocity ( r for adipose=0.39, r for discontinuity=0.45, r for collagen=0.26) and electrogram amplitude ( r for adipose=0.73, r for contiguity=0.77, r for collagen=0.68) compared with collagen. Collagen density was similar between the MI+ groups ( P >0.29). However, the MI+VT+ group demonstrated a significant (all P ≤0.01) increase in adipose (8%) and discontinuity (qualitative) and decrease in conduction velocity (13%) and electrogram amplitude (21%) at MI borders compared with the MI+VT− group. In scar, myocytes adjacent to fibrofatty interfaces demonstrated increased connexin43 lateralization. A gradient increase in adipose was observed at sites that supported preferential presystolic VT activation and exhibited attenuation of excitation wavelength ( P <0.001). Conclusions— Intramyocardial adiposity, in association with myocardial discontinuity within left ventricular scar borders, is a significant factor associated with altered electrophysiological properties, aberrant connexin43 expression, and increased propensity for VT after MI. # Clinical Perspective {#article-title-48}