BACKGROUND The decision to abandon or extract superfluous sterile leads is controversial. OBJECTIVE The purpose of this study was to compare procedural outcomes and long-term survival of patients with and those without abandoned leads undergoing lead extraction (LE). METHODS Retrospective review of all patients who had undergone transvenous LE at our institution from January 2007 to May 2016 was performed. Patients were stratified into 2 groups based on the presence (group 1) or absence (group 2) of abandoned leads. < p > RESULTS Among 774 patients who had undergone LE procedures, 38 (4.9%) had abandoned leads (group 1). Dwell time of the oldest extracted lead was longer in group 1 vs group 2 (7.6 +/- 4.9 years vs 5.6 +/- 4.4 years; P = .017), as was infection as an indication for LE (76% vs 33%; P <.001). A bailout femoral approach was more commonly required in group 1 than in group 2 (18.4% vs 6%; P = .007). Complete procedural success rates were similar (92.1% CONCLUSION Abandoned leads at the time of LE were associated with increased procedural complexity, including a higher rate of bailout femoral extraction, and may be associated with lower clinical success. Among appropriately selected patients, consideration should be given to LE instead of abandonment.

PurposeTo develop a Shared K‐space (SharK) magnetic resonance imaging (MRI) sequence that combines angiographic and late gadolinium enhancement (LGE) acquisitions to improve atrial wall segmentation and scar identification, and to develop a novel visualization method that quantifies scar encirclement of pulmonary veins postablation treatment for atrial fibrillation.Materials and MethodsA SharK sequence was developed and used at 3T to image the left atrium in 11 patients postcryoballoon ablation. The effects of sharing k‐space between the angiographic and LGE acquisitions on the accuracy of scar were assessed. The left atrial wall was segmented and points about each pulmonary vein (PV) ostia were projected onto a bullseye to quantitatively compare PV encirclement. The parameters used to quantify encirclement were varied to perform a sensitivity analysis.ResultsCompared to using a complete set of k‐space, total atrial scar differences were significant only when sharing >75% k‐space (P = 0.014), and 90% sensitivity and specificity for identifying scar was achieved when sharing 50% k‐space. In patients, the right PVs showed more intersubject variance in encirclement compared to the left PVs. A 100° anteroinferior portion of the left PVs was always encircled, while the superior segments of both right PVs was ablated in only 6/11 patients.ConclusionA SharK sequence was developed to combine angiographic and LGE imaging for atrial wall segmentation and scar identification. The PV bullseye quantifies and localizes encirclement about the PVs. The left PVs showed a higher amount of scar encirclement and less variability compared to the right PVs.Level of Evidence: 2Technical Efficacy: Stage 1J. Magn. Reson. Imaging 2018;47:477–486.

Key Teaching Points•Subcutaneous implantable cardioverter-defibrillators (S-ICD) can be implanted safely in patients with deep brain stimulators (DBS).•DBS could affect sensing in patients with S-ICD.•Changing sensing vectors on the S-ICD could overcome sensing abnormalities due to device–device interaction in this setting. •Subcutaneous implantable cardioverter-defibrillators (S-ICD) can be implanted safely in patients with deep brain stimulators (DBS).•DBS could affect sensing in patients with S-ICD.•Changing sensing vectors on the S-ICD could overcome sensing abnormalities due to device–device interaction in this setting.

Frontiers in Fontan Failure was the title of a 2015 conference sponsored by Children's Healthcare of Atlanta and Emory University School of Medicine. In what is hoped to be the first of many such gatherings, speakers and attendees gathered to discuss the problem of long-term clinical deterioration in these patients. Specific focuses included properly defining the problem and then discussing different treatment strategies, both medical and surgical. The health of the liver after Fontan palliation was a particular point of emphasis, as were quality of life and future directions.

Heart disease is a leading cause of death in adults. Here, we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this signaling is antagonized by the chymase, mouse mast cell protease 4 (MMCP-4), which degrades IGF-1. We found that deletion of the gene encoding MMCP-4 (Mcpt4), markedly reduced late, but not early, infarct size by suppressing IGF-1 degradation and, consequently, diminished cardiac dysfunction and adverse structural remodeling. Our findings represent the first demonstration to our knowledge of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in post-ischemic heart disease.

Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT1R) and type-2 (AT2R) receptors, which have opposing effects. AT2R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT2Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT2Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 µg/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echocardiography. Immunohistochemistry was performed to localize and quantify AT2Rs and p-Ser(1177)-endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT2R and peroxisome proliferator-activated receptor-γ (PPAR-γ), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT2R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an ~6-fold increase in VSMC PPAR-γ levels (P < 0.001) and the AT2R-mediated hypotension was abolished by GW-9662. AT2R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT2R expression by ~6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT2R-mediated hypotensive response that involves PPAR-γ, and is down regulated by a HCD.

Heart disease is a leading cause of death in adults. Here we show that a few days after coronary artery ligation and reperfusion, the ischemia-injured heart elaborates the cardioprotective polypeptide, insulin-like growth factor-1 (IGF-1), which activates IGF-1 receptor prosurvival signaling and improves cardiac left ventricular systolic function. However, this is antagonized by the chymase, mouse mast cell protease-4 (MMCP-4), which degrades IGF-1 (Fig. 1). We found that MMCP-4 deficiency, resulted in sustained IGF-1 levels and IGF-1 receptor prosurvival signaling post-I/R. MMCP-4 deficiency markedly reduced late, but not early, infarct size (~50% reduction: n=5-7, p value= 0.001) by suppressing IGF-1 degradation and, consequently, improving cardiac function (EF: 26% greater, n=21, p value= 0.001) and adverse structural remodeling (Fig. 2). Our findings represent the first demonstration of tissue IGF-1 regulation through proteolytic degradation and suggest that chymase inhibition may be a viable therapeutic approach to enhance late cardioprotection in post-ischemic heart disease.

It is widely believed that perinatal cardiomyocyte terminal differentiation blocks cytokinesis, thereby causing binucleation and limiting regenerative repair after injury. This suggests that heart growth should occur entirely by cardiomyocyte hypertrophy during preadolescence when, in mice, cardiac mass increases many-fold over a few weeks. Here, we show that a thyroid hormone surge activates the IGF-1/IGF-1-R/Akt pathway on postnatal day 15 and initiates a brief but intense proliferative burst of predominantly binuclear cardiomyocytes. This proliferation increases cardiomyocyte numbers by ~40%, causing a major disparity between heart and cardiomyocyte growth. Also, the response to cardiac injury at postnatal day 15 is intermediate between that observed at postnatal days 2 and 21, further suggesting persistence of cardiomyocyte proliferative capacity beyond the perinatal period. If replicated in humans, this may allow novel regenerative therapies for heart diseases.

Mast cell chymase (CHY), a multifunctional protease with Ang II-forming activity, garnered interest due to the success of angiotensin converting enzyme inhibitors (ACEi) in the treatment of heart failure. The VALIANT trial evaluated the contribution of this alternate Ang II pathway by adding an AT 1 Ang II receptor blocker (ARB) to an ACEi post-myocardial infarction (MI), but the combination showed no additional benefit, suggesting CHY was unimportant post-MI. However, the role of CHY, independent of its Ang II-forming activity, remains unaddressed. To test this, we first re-evaluated the role of CHY-generated Ang II by blocking the effects of ACE+CHY-generated Ang II using an ACEi+ARB+AT 2 receptor blocker (PD122139) combination (AAA), and compared this to ACEi monotherapy in wild-type (WT) mice. We then addressed the Ang II-independent role of CHY by comparing these therapies in chymase (MMCP-4)-deficient (KO) vs WT mice. WT and KO mice (N=10-20) underwent sham or MI (90-min ischemia-reperfusion) surgery, and were treated daily with vehicle (Veh), ACEi, or AAA 24h post reperfusion. After 14 days, echocardiographic and hemodynamic analyses indicated no significant inter-genotype differences in sham animals. In post-MI WT mice, ACEi vs Veh resulted in improved ejection fraction (EF) (34±1.8% vs 28±1.7%; p<0.05) and reduced LV end-diastolic dimension (LVEDD) (4.2+0.09 mm vs 4.7±0.1 mm; p<0.05). However, AAA did not result in further improvements in either parameter as compared to ACEi, suggesting that CHY-generated Ang II is unimportant post-MI, confirming VALIANT. While the initial (24-h post-MI) infarct sizes were similar between genotypes (WT: 63±5% vs KO: 65±2% infarct as percent of area at risk; p=0.6), EF was superior in KO vs WT mice in all treatment groups (36±3% vs 28±2% (Veh); 47±3% vs 34±2% (ACEi); 49±3% vs 36±3% (AAA); p<0.05). Further, LV dilatation was also more pronounced in WT mice (LVEDD: 4.7±0.4 mm, WT-Veh vs 4.3±0.5 mm, KO-Veh; p<0.05). ACEi decreased mean arterial pressure post-MI (p<0.01), but not differentially in WT vs KO (Veh: 70±5 mmHg vs 66±3 mmHg; p=0.47; ACEi: 48±3.7 mmHg vs 38±4.8 mmHg; N=6−10; p=0.1). Thus, we conclude that CHY, independent of Ang II, is a potential therapeutic target for the treatment of the post-MI heart.