Perioperative considerations during implantation of the subcutaneous defibrillator: State-of-the-art review.

The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an important tool in the armamentarium of an electrophysiologist. Multiple randomized trials over the last decade have shown that S-ICDs are as efficacious as the transvenous ICDs and eliminate complications related to vascular access. In this review, we highlight issues unique to S-ICD implantation, focusing not only on the surgical implantation procedure, but also the pre- and postimplant management of the patient.

Characterization of pleural effusion after left atrial appendage exclusion using the Lariat procedure.

BACKGROUND: The Lariat procedure is increasingly used for the exclusion of the left atrial appendage (LAA) in atrial fibrillation (AF) patients. There are anecdotal reports of pleural effusions after the Lariat procedure. However, the incidence, demographics, and pathophysiology of these effusions are largely unknown. OBJECTIVE: Characterization of pleural effusions in patients who underwent LAA exclusion using the Lariat procedure. METHODS: We report the incidence, demographics, and clinical and laboratory characteristics of patients from a multicenter prospective registry who underwent the Lariat procedure and subsequently developed pleural effusions. RESULTS: A total of 10 out of 310 (3.2%) patients developed significant pleural effusions after the Lariat procedure. The mean age of these patients was 67 ± 9, ranging from 52 to 78 years and included 5 (50%) males. Nine patients had persistent AF with median CHADS2 score of 2.7 ± 1.2. The LAA was successfully ligated in all these patients. Post-Lariat procedure, 6 patients developed bilateral and 4 patients developed left-sided pleural effusions. Pleural tap revealed transudative in 2 and exudative in 6 patients. The remaining 2 patients responded to active diuresis and behaved clinically like transudative effusions. There is a statistically significant difference between the onset of pleural effusion after the Lariat procedure between tPLE versus ePLE groups (14 ± 1.2 vs. 6 ± 6, P = 0.05). CONCLUSION: Incidence of clinically significant pleural effusion is uncommon after the Lariat procedure and can be either exudative or transudative in nature depending on the underlying mechanisms. More prospective studies are needed to study the pathophysiologic basis of development of pleural effusions after the Lariat procedure.

Left Atrial Appendage Closure and Systemic Homeostasis: The LAA HOMEOSTASIS Study.

BACKGROUND: The impact of left atrial appendage (LAA) exclusion, comparing an epicardial LAA or an endocardial LAA device, on systemic homeostasis remains unknown. OBJECTIVES: This study compared the effects of epicardial or endocardial LAA devices on the neurohormonal profiles of patients, emphasizing the roles of the renin-angiotensin-aldosterone system and the autonomic nervous system. METHODS: This is a prospective, single-center, observational study including 77 patients who underwent LAA closure by an epicardial (n = 38) or endocardial (n = 39) device. Key hormones involved in the adrenergic system (adrenaline, noradrenaline), renin-angiotensin-aldosterone system (aldosterone, renin), metabolic system (adiponectin, free fatty acids, insulin, ß-hydroxybutyrate, and free glycerols), and natriuresis (atrial and B-type natriuretic peptides) were assessed immediately before the procedure, immediately after device deployment, at 24 h, and at 3 months follow-up. RESULTS: In the endocardial LAA device group, when compared with baseline blood adrenaline, noradrenaline and aldosterone were significantly lower at 24 h and 3 months (p < 0.05). There was no significant change in levels post-endocardial LAA device implantation. After epicardial LAA device implantation, there were significant increases in adiponectin and insulin, with decreased free fatty acids at 3 months. There was no significant change in these levels post-endocardial LAA device. N-terminal pro-A-type natriuretic peptide and N-terminal pro-B-type natriuretic peptide were significantly decreased in the acute phase after epicardial LAA device implantation, which subsequently normalized at 3 months. Post endocardial LAA device implantation, the levels increased immediately and normalized after 24 h. Systemic blood pressure was also significantly lower at all time points after epicardial LAA device implantation, which was not seen post-endocardial LAA device implantation. CONCLUSIONS: There are substantial differences in hemodynamics and neurohormonal effects of LAA exclusion with epicardial and endocardial devices. Further studies are required to elucidate the underlying mechanism of these physiological changes.

Atrial Tachycardias After Surgical Atrial Fibrillation Ablation: Clinical Characteristics, Electrophysiological Mechanisms, and Ablation Outcomes From a Large, Multicenter Study.

OBJECTIVES: The clinical characteristics, electrophysiological mechanisms, and ablation outcomes of post-surgical atrial fibrillation ablation (SAFA) atrial tachycardias (ATs) have not been studied in a large, multicenter cohort. BACKGROUND: ATs are often seen following SAFA. METHODS: Analysis was performed on 137 patients (age, 62 ± 10 years; 74% male) who underwent catheter ablation for symptomatic post-SAFA AT from 2004 to 2013 at 3 high-volume institutions in the United States. RESULTS: A total of 137 patients had 149 ATs that were mapped; 103 (69%) had a left atrial (LA) origin and 46 (31%) had a right atrial origin. Of the 149, a total of 44 (30%) had a focal mechanism, with 29 (66%) having an LA origin, with 53% localized to LA posterior wall. Of the 105 re-entrant ATs, 74 (71%) were of LA origin. The predominant circuits were cavotricuspid isthmus (n = 25), perimitral (n = 19), LA roof (n = 17), left pulmonary veins (n = 13), right pulmonary vein/LA septum (n = 12), and LA appendage (n = 7). A total of 93% of patients had ≥1 pulmonary vein reconnection requiring reisolation. Catheter ablation resulted in termination and noninducibility of 97% of right atrial and 93% of LA ATs. Over a 12-month follow-up, 80% of patients were free of any AT or AF. CONCLUSIONS: In this large multicenter cohort of post-SAFA ATs, most were of LA origin, with macro-re-entry being the most common arrhythmia mechanism. Wide variability in location of AT circuits was seen in both right atrial and LA and likely reflects underlying arrhythmogenic substrate and differences in modified SAFA techniques. Catheter ablation was highly successful in eliminating the culprit AT with favorable long-term outcomes.

Non-hypoxic stabilization of HIF-Iα during coordinated interaction between Akt and angiopoietin-1 enhances endothelial commitment of bone marrow stem cells.

We previously reported that mesenchymal stem cells (MSC) co-expressing Akt and angiopoietin-1 (Ang-1) preserved infarcted heart function via angiomyogenesis. The present study determined the mechanism of co-overexpression of Akt and Ang-1 in promoting endothelial commitment of MSC. The cells were transduced with vectors encoding for Akt ((Akt)MSC), Ang-1 ((Ang-1)MSC), and both Akt and Ang-1 ((AA)MSC) using Empty vector transduced MSC ((Emp)MSC) as control. Molecular studies indicated a coordinated interaction between Akt and Ang-1 in (AA)MSC and led to non-hypoxic stabilization of hypoxia inducible factor-1α (HIF-Iα) which accentuated under 4-h anoxia. We also observed HIF-Iα dependent induction of hemeoxygenase-1, endothelial specific markers and VEGF in (AA)MSC. Vascular commitment of (AA)MSC was confirmed by immunostaining, Western blotting and flow cytometry for endothelial specific early and late markers including Flt1, Flk1, Tie2, VCAM-1, and von Willebrand Factor-VIII (vWF-VIII) in HIF-Iα dependent fashion besides exhibiting higher emigrational activity and angiogenesis in vitro. (AA)MSC transplanted into rat model of myocardial infarction showed higher Flk1 and Flt1 positivity and also promoted intrinsic Flk1(+) and Flt1(+) cell mobilization into the infarcted heart. Given the ease of availability of MSC and simplicity of approach to co-overexpress Ang-1 and Akt to enhance their endothelial commitment, the strategy will be significant for cellular angiogenesis to treat ischemic heart.

Sonic Hedgehog gene delivery to the rodent heart promotes angiogenesis via iNOS/netrin-1/PKC pathway.

BACKGROUND: We hypothesized that genetic modification of mesenchymal stem cells (MSCs) with Sonic Hedgehog (Shh) transgene, a morphogen during embryonic development and embryonic and adult stem cell growth, improved their survival and angiogenic potential in the ischemic heart via iNOS/netrin/PKC pathway. METHODS/PRINCIPAL FINDINGS: MSCs from young Fisher-344 rat bone marrow were purified and transfected with pCMV Shh plasmid ((Shh)MSCs). Immunofluorescence, RT-PCR and Western blotting showed higher expression of Shh in (Shh)MSCs which also led to increased expression of angiogenic and pro-survival growth factors in (Shh)MSCs. Significantly improved migration and tube formation was seen in (Shh)MSCs as compared to empty vector transfected MSCs ((Emp)MSCs). Significant upregulation of netrin-1 and iNOS was observed in (Shh)MSCs in PI3K independent but PKC dependent manner. For in vivo studies, acute myocardial infarction model was developed in Fisher-344 rats. The animals were grouped to receive 70 microl basal DMEM without cells (group-1) or containing 1x10(6) (Emp)MSCs (group-2) and (Shh)MSCs (group-3). Group-4 received recombinant netrin-1 protein injection into the infarcted heart. FISH and sry-quantification revealed improved survival of (Shh)MSCs post engraftment. Histological studies combined with fluorescent microspheres showed increased density of functionally competent blood vessels in group-3 and group-4. Echocardiography showed significantly preserved heart function indices post engraftment with (Shh)MSCs in group-3 animals. CONCLUSIONS/SIGNIFICANCE: Reprogramming of stem cells with Shh maximizes their survival and angiogenic potential in the heart via iNOS/netrin-1/PKC signaling.