Superior-Type Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Phenotype Mimicking the Slow-Fast Type.

BACKGROUND: Superior-type fast-slow (sup-F/S-) atrioventricular nodal reentrant tachycardia (AVNRT) is a rare AVNRT variant using a superior slow pathway (SP) as the retrograde limb. Its intracardiac appearance, characterized by a short atrio-His (AH) interval and the earliest site of atrial activation in the His-bundle, is an initial indicator for making a diagnosis. METHODS: Among 22 consecutive patients with sup-F/S-AVNRT, 3 (age, 68-81 years) patients had an apparent slow-fast (S/F-) AVNRT characterized by a long AH interval and the earliest site of atrial activation in or superior to the His-bundle region (tachy-long-AH). RESULTS: The diagnosis of sup-F/S-AVNRT was based on the standard criteria in 2 patients and on the occurrence of Wenckebach-type atrioventricular block during tachycardia, which was attributable to a block at the lower common pathway (LCP) below the circuit of the AVNRT, detected owing to the lower common pathway potentials, in one patient. As with the typical S/F-AVNRT, tachy-long-AH was induced after a jump in the AH interval. In contrast to typical S/F-AVNRT, fluctuation in the ventriculoatrial interval was observed during the tachy-long-AH. Ventricular overdrive pacing was unable to entrain or terminate the tachy-long-AH. Moreover, the tachy-long-AH reciprocally transited to/from sup-F/S-AVNRT spontaneously or was triggered by ventricular contractions while the atrial cycle length and earliest site of atrial activation remained unchanged. Both tachycardias were cured by ablation at a single site in the right-side para-Hisian region of 2 patients and the noncoronary aortic cusp of one patient. Collectively, the essential circuit of both tachycardias was identical, and the tachy-long-AH was diagnosed as another phenotype of sup-F/S-AVNRT accompanied by sustained antegrade conduction via another bystander slow pathway breaking through the His-bundle owing to the repetitive antegrade block at the lower common pathway, thus representing a long AH interval during the ongoing sup-F/S-AVNRT. CONCLUSIONS: An unknown sup-F/S-AVNRT phenotype exists that apparently mimics the typical S/F-AVNRT and is also an unknown subtype of apparent S/F-AVNRT.

Unique electrophysiological properties of fast-slow atrioventricular nodal reentrant tachycardia characterized by a shortening of retrograde conduction time via a slow pathway manifested during atrial induction.

INTRODUCTION: Electrophysiological properties of reentry circuits of fast-slow atrioventricular nodal reentrant tachycardia (F/S-AVNRT) may contribute to cyclic variability after atrial induction. METHODS: In 156 atrial inductions of 33 patients with F/S-AVNRT, we measured the atrio-His (AH) and His-atrial (HA) intervals in the first cycle after the induction (AH[1] and HA[1], respectively), those in the second cycle (AH [2] and HA [2], respectively), and those during tachycardia that maintained a stable cycle length AH[T] and HA[T], respectively), and calculated the value of AH(1) minus AH(T) [ΔAH] and the value of HA(1) minus HA(T) [ΔHA] in each induction. According to the sum of ΔAH and ΔHA, tachycardia variability was classified as incremental (<-20), balanced (-20 to 20), or decremental (>20). RESULTS: ΔAH and ΔHA were significantly different between the three responses: 6 ± 28 and -67 ± 39 in 55 inductions (35%) with an incremental response, 20 ± 10 and -23 ± 28 in 59 (38%) with a balanced response, and 54 ± 44 and 4 ± 50 in 42 (27%) with a decremental response, respectively. Incremental response was reproducibly and consistently observed in 33% of patients. HA(2) was similar to HA(T) in inductions with an incremental response. These results suggest that incremental response can be manifested only in the first cycle when HA(1) is excessively shortened, approximating a retrograde conduction time over a slow pathway, in contrast, and far superior to a decremental delay of AH(1). CONCLUSION: In specific patients with F/S-AVNRT, poorly recognized, electrophysiological properties of shortening a retrograde conduction time over a slow pathway was manifested during atrial induction.

Atypical Fast-Slow Atrioventricular Nodal Reentrant Tachycardia Using a Slow Pathway Extending to the Superoanterior Right Atrium.

We report a case of atypical fast-slow atrioventricular nodal reentrant tachycardia (AVNRT) using a slow pathway variant extending to the superoanterior right atrium. The AVNRT diagnosis was confirmed by using standard electrophysiological criteria that exclude a diagnosis of atrial tachycardia and atrioventricular reentrant tachycardia. The earliest atrial activation during tachycardia was found in the superoanterior right atrium adjacent to the tricuspid annulus, where the first delivery of radiofrequency energy terminated and eliminated the inducibility of the tachycardia.

Glucose is preferentially utilized for biomass synthesis in pressure-overloaded hearts: evidence from fatty acid-binding protein-4 and -5 knockout mice.

Aims: The metabolism of the failing heart is characterized by an increase in glucose uptake with reduced fatty acid (FA) oxidation. We previously found that the genetic deletion of FA-binding protein-4 and -5 [double knockout (DKO)] induces an increased myocardial reliance on glucose with decreased FA uptake in mice. However, whether this fuel switch confers functional benefit during the hypertrophic response remains open to debate. To address this question, we investigated the contractile function and metabolic profile of DKO hearts subjected to pressure overload. Methods and results: Transverse aortic constriction (TAC) significantly reduced cardiac contraction in DKO mice (DKO-TAC), although an increase in cardiac mass and interstitial fibrosis was comparable with wild-type TAC (WT-TAC). DKO-TAC hearts exhibited enhanced glucose uptake by 8-fold compared with WT-TAC. Metabolic profiling and isotopomer analysis revealed that the pool size in the TCA cycle and the level of phosphocreatine were significantly reduced in DKO-TAC hearts, despite a marked increase in glycolytic flux. The ingestion of a diet enriched in medium-chain FAs restored cardiac contractile dysfunction in DKO-TAC hearts. The de novo synthesis of amino acids as well as FA from glycolytic flux was unlikely to be suppressed, despite a reduction in each precursor. The pentose phosphate pathway was also facilitated, which led to the increased production of a coenzyme for lipogenesis and a precursor for nucleotide synthesis. These findings suggest that reduced FA utilization is not sufficiently compensated by a robust increase in glucose uptake when the energy demand is elevated. Glucose utilization for sustained biomass synthesis further enhances diminishment of the pool size in the TCA cycle. Conclusions: Our data suggest that glucose is preferentially utilized for biomass synthesis rather than ATP production during pressure-overload-induced cardiac hypertrophy and that the efficient supplementation of energy substrates may restore cardiac dysfunction caused by energy insufficiency.

[Vascular Calcification - Pathological Mechanism and Clinical Application - . Role of vascular smooth muscle cells in vascular calcification].

Vascular calcification is commonly seen with aging, chronic kidney disese (CKD), diabetes, and atherosclerosis, and is closely associated with cardiovascular morbidity and mortality. Vascular calcification has long been regarded as the final stage of degeneration and necrosis of arterial wall and a passive, unregulated process. However, it is now known to be an active and tightly regulated process involved with phenotypic transition of vascular smooth muscle cells (VSMC) that resembles bone mineralization. Briefly, calcium deposits of atherosclerotic plaque consist of hydroxyapatite and may appear identical to fully formed lamellar bone. By using a genetic fate mapping strategy, VSMC of the vascular media give rise to the majority of the osteochondrogenic precursor- and chondrocyte-like cells observed in the calcified arterial media of MGP (- / -) mice. Osteogenic differentiation of VSMC is characterized by the expression of bone-related molecules including bone morphogenetic protein (BMP) -2, Msx2 and osteopontin, which are produced by osteoblasts and chondrocytes. Our recent findings are that (i) Runx2 and Notch1 induce osteogenic differentiation, and (ii) advanced glycation end-product (AGE) /receptor for AGE (RAGE) and palmitic acid promote osteogenic differentiation of VSMC. To understand of the molecular mechanisms of vascular calcification is now under intensive research area.

Remarkable regression of massive deep vein thrombosis in response to intensive oral rivaroxaban treatment.

Deep vein thrombosis (DVT) is a common disease and is associated with pulmonary embolism (PE). Proximal iliofemoral DVT may lead to severe PE and chronic venous insufficiency. The standard therapy for DVT is anticoagulant therapy using heparin and a vitamin K antagonist, but a recent clinical study showed that rivaroxaban, an oral Xa inhibitor, was comparable to standard therapy and had less bleeding complications. Intensive high-dose anticoagulation is recommended during the initial 3 weeks of DVT treatment. The present report describes a case of a 77-year-old male showing a remarkable regression of DVT in response to rivaroxaban treatment within the initial 3 weeks of therapy and who did not experience any adverse events. His DVT was massive and was accompanied by proximal iliofemoral vein thrombus and iliac vein compression syndrome. Rivaroxaban, especially in intensive high-dose treatment, might be a safe and effective therapeutic choice for massive DVT.

A Case of Type 2 Amiodarone-Induced Thyrotoxicosis That Underwent Total Thyroidectomy under High-Dose Steroid Administration.

Amiodarone is used commonly and effectively in the treatment of arrhythmia; however, it may cause thyrotoxicosis categorized into two types: iodine-induced hyperthyroidism (type 1 amiodarone-induced thyrotoxicosis (AIT)) and destructive thyroiditis (type 2 AIT). We experienced a case of type 2 AIT, in which high-dose steroid was administered intravenously, and we finally decided to perform total thyroidectomy, resulting in a complete cure of the AIT. Even though steroid had been administered to the patient (maximum 80 mg of prednisolone), the operation was performed safely and no acute adrenal crisis as steroid withdrawal syndrome was found after the operation. Few cases of type 2 AIT that underwent total thyroidectomy with high-dose steroid administration have been reported. The current case suggests that total thyroidectomy should be taken into consideration for patients with AIT who cannot be controlled by medical treatment and even in those under high-dose steroid administration.

Airway uric acid is a sensor of inhaled protease allergens and initiates type 2 immune responses in respiratory mucosa.

Although type 2 immune responses to environmental Ags are thought to play pivotal roles in asthma and allergic airway diseases, the immunological mechanisms that initiate the responses are largely unknown. Many allergens have biologic activities, including enzymatic activities and abilities to engage innate pattern-recognition receptors such as TLR4. In this article, we report that IL-33 and thymic stromal lymphopoietin were produced quickly in the lungs of naive mice exposed to cysteine proteases, such as bromelain and papain, as a model for allergens. IL-33 and thymic stromal lymphopoietin sensitized naive animals to an innocuous airway Ag OVA, which resulted in production of type 2 cytokines and IgE Ab, and eosinophilic airway inflammation when mice were challenged with the same Ag. Importantly, upon exposure to proteases, uric acid (UA) was rapidly released into the airway lumen, and removal of this endogenous UA by uricase prevented type 2 immune responses. UA promoted secretion of IL-33 by airway epithelial cells in vitro, and administration of UA into the airways of naive animals induced extracellular release of IL-33, followed by both innate and adaptive type 2 immune responses in vivo. Finally, a potent UA synthesis inhibitor, febuxostat, mitigated asthma phenotypes that were caused by repeated exposure to natural airborne allergens. These findings provide mechanistic insights into the development of type 2 immunity to airborne allergens and recognize airway UA as a key player that regulates the process in respiratory mucosa.

Pseudo-postpacing interval of diastolic potential after entrainment pacing of remote bystander pathway in reentrant ventricular tachycardia.

After entrainment pacing, the postpacing interval of a diastolic potential may be misinterpreted if the distal tip of the ablation catheter captures a remote bystander pathway adjacent to the critical isthmus of a complex reentrant circuit in a structurally diseased heart. We discuss this possible pitfall of entrainment mapping of reentrant ventricular tachycardia, observed after a healed myocardial infarction.

Electroanatomically estimated length of slow pathway in atrioventricular nodal reentrant tachycardia.

The length of the slow pathway (SP-L) in atrioventricular (AV) nodal reentrant tachycardia (NRT) has never been measured clinically. We studied the relationship among (a) SP-L, i.e., the distance between the most proximal His bundle (H) recording and the most posterior site of radiofrequency (RF) delivery associated with a junctional rhythm, (b) the length of Koch's triangle (Koch-L), (c) the conduction time over the slow pathway (SP-T), measured by the AH interval during AVNRT at baseline, and (d) the distance between H and the site of successful ablation (SucABL-L) in 26 women and 20 men (mean age 64.6 ± 11.6 years), using a stepwise approach and an electroanatomic mapping system (EAMS). SP-L (15.0 ± 5.8 mm) was correlated with Koch-L (18.6 ± 5.6 mm; R 2 = 0.1665, P < 0.005), SP-T (415 ± 100 ms; R 2 = 0.3425, P = 0.036), and SucABL-L (11.6 ± 4.7 mm; R 2 = 0.5243, P < 0.0001). The site of successful ablation was located within 10 mm of the posterior end of the SP in 38 patients (82.6 %). EAMS-guided RF ablation, using a stepwise approach, revealed individual variations in SP-L related to the size of Koch's triangle and AH interval during AVNRT. Since the site of successful ablation was also correlated with SP-L and was usually located near the posterior end of the SP, ablating anteriorly, away from the posterior end, is not a prerequisite for the success of ablation procedures.

Peroxisome proliferator-activated receptor-γ in capillary endothelia promotes fatty acid uptake by heart during long-term fasting.

BACKGROUND: Endothelium is a crucial blood-tissue interface controlling energy supply according to organ needs. We investigated whether peroxisome proliferator-activated receptor-γ (PPARγ) induces expression of fatty acid-binding protein 4 (FABP4) and fatty acid translocase (FAT)/CD36 in capillary endothelial cells (ECs) to promote FA transport into the heart. METHODS AND RESULTS: Expression of FABP4 and CD36 was induced by the PPARγ agonist pioglitazone in human cardiac microvessel ECs (HCMECs), but not in human umbilical vein ECs. Real-time PCR and immunohistochemistry of the heart tissue of control (Pparg(fl/null)) mice showed an increase in expression of FABP4 and CD36 in capillary ECs by either pioglitazone treatment or 48 hours of fasting, and these effects were not found in mice deficient in endothelial PPARγ (Pparg(▵)(EC)(/null)). Luciferase reporter constructs of the Fabp4 and CD36 promoters were markedly activated by pioglitazone in HCMECs through canonical PPAR-responsive elements. Activation of PPARγ facilitated FA uptake by HCMECs, which was partially inhibited by knockdown of either FABP4 or CD36. Uptake of an FA analogue, (125)I-BMIPP, was significantly reduced in heart, red skeletal muscle, and adipose tissue in Pparg(▵)(EC)(/null) mice as compared with Pparg(fl/null) mice after olive oil loading, whereas those values were comparable between Pparg(fl/null) and Pparg(▵)(EC)(/null) null mice on standard chow and a high-fat diet. Furthermore, Pparg(▵)(EC)(/null) mice displayed slower triglyceride clearance after olive oil loading. CONCLUSIONS: These findings identified a novel role for capillary endothelial PPARγ as a regulator of FA handing in FA-metabolizing organs including the heart in the postprandial state after long-term fasting.

Characteristics of systolic and diastolic potentials recorded in the left interventricular septum in verapamil-sensitive left ventricular tachycardia.

We studied the electrophysiological characteristics of systolic (SP) and diastolic (DP) potentials recorded during sinus rhythm (SR) in the left interventricular septum of a 27 year-old woman presenting with verapamil-sensitive idiopathic left ventricular tachycardia (VT). During SR, and during VT, SP was activated from ventricular base-to-apex, and DP from apex-to-base. SP and DP were both detected at the site of successful ablation during SR, whereas during VT, DP was detected away from the earliest activation site. Thus, SP apparently reflected a critical component of the reentrant circuit, while DP reflected the activation of a bystander pathway.