Longitudinal QTc stability and impact of baseline cardiac rhythm on discharge dose in dofetilide-treated patients.

INTRODUCTION: Dofetilide suppresses atrial fibrillation (AF) in a dose-dependent fashion. The protective effect of AF against QTc prolongation induced torsades de pointe and transient post-cardioversion QTc prolongation may result in dofetilide under-dosing during initiation. Thus, the optimal timing of cardioversion for AF patients undergoing dofetilide initiation to optimize discharge dose remains unknown as does the longitudinal stability of QTc . The purpose of this study was to evaluate the impact of baseline rhythm on dofetilide dosing during initiation and assess the longitudinal stability of QTc-all (Bazzett, Fridericia, Framingham, and Hodges) over time. METHODS: Medical records of patients who underwent preplanned dofetilide loading at a tertiary care center between January 2016 and 2019 were reviewed. RESULTS: A total of 198 patients (66 ± 10 years, 32% female, CHADS2 -Vasc 3 [2-4]) presented for dofetilide loading in either AF (59%) or sinus rhythm (SR) (41%). Neither presenting rhythm, nor spontaneous conversion to SR impacted discharge dose. The cumulative dofetilide dose before cardioversion moderately correlated (r = .36; p = .0001) with discharge dose. Postcardioversion QTc-all prolongation (p < .0001) prompted discharge dose reduction (890 ± 224 mcg vs. 552 ± 199 mcg; p < .0001) in 30% patients. QTc-all in SR prolonged significantly during loading (p < .0001). All patients displayed QTc-all reduction (p < .0001) from discharge to short-term (46 [34-65] days) that continued at long-term (360 [296-414] days) follow-ups. The extent of QTc-all reduction over time moderately correlated with discharge QTc-all (r = .54-0.65; p < .0001). CONCLUSION: Dofetilide initiation before cardioversion is equivalent to initiation during SR. Significant QTc reduction proportional to discharge QTc is seen over time in all dofetilide-treated patients. QTc returns to preloading baseline during follow-up in patients initiated in SR.

Kv1.3 channels facilitate the connection between metabolism and blood flow in the heart.

The connection between metabolism and flow in the heart, metabolic dilation, is essential for cardiac function. We recently found redox-sensitive Kv1.5 channels play a role in coronary metabolic dilation; however, more than one ion channel likely plays a role in this process as animals null for these channels still showed limited coronary metabolic dilation. Accordingly, we examined the role of another Kv1 family channel, the energetically linked Kv1.3 channel, in coronary metabolic dilation. We measured myocardial blood flow (contrast echocardiography) during norepinephrine-induced increases in cardiac work (heart rate x mean arterial pressure) in WT, WT mice given correolide (preferential Kv1.3 antagonist), and Kv1.3-null mice (Kv1.3-/- ). We also measured relaxation of isolated small arteries mounted in a myograph. During increased cardiac work, myocardial blood flow was attenuated in Kv1.3-/- and in correolide-treated mice. In isolated vessels from Kv1.3-/- mice, relaxation to H2 O2 was impaired (vs WT), but responses to adenosine and acetylcholine were equivalent to WT. Correolide reduced dilation to adenosine and acetylcholine in WT and Kv1.3-/- , but had no effect on H2 O2 -dependent dilation in vessels from Kv1.3-/- mice. We conclude that Kv1.3 channels participate in the connection between myocardial blood flow and cardiac metabolism.

Requisite Role of Kv1.5 Channels in Coronary Metabolic Dilation.

RATIONALE: In the working heart, coronary blood flow is linked to the production of metabolites, which modulate tone of smooth muscle in a redox-dependent manner. Voltage-gated potassium channels (Kv), which play a role in controlling membrane potential in vascular smooth muscle, have certain members that are redox-sensitive. OBJECTIVE: To determine the role of redox-sensitive Kv1.5 channels in coronary metabolic flow regulation. METHODS AND RESULTS: In mice (wild-type [WT], Kv1.5 null [Kv1.5(-/-)], and Kv1.5(-/-) and WT with inducible, smooth muscle-specific expression of Kv1.5 channels), we measured mean arterial pressure, myocardial blood flow, myocardial tissue oxygen tension, and ejection fraction before and after inducing cardiac stress with norepinephrine. Cardiac work was estimated as the product of mean arterial pressure and heart rate. Isolated arteries were studied to establish whether genetic alterations modified vascular reactivity. Despite higher levels of cardiac work in the Kv1.5(-/-) mice (versus WT mice at baseline and all doses of norepinephrine), myocardial blood flow was lower in Kv1.5(-/-) mice than in WT mice. At high levels of cardiac work, tissue oxygen tension dropped significantly along with ejection fraction. Expression of Kv1.5 channels in smooth muscle in the null background rescued this phenotype of impaired metabolic dilation. In isolated vessels from Kv1.5(-/-) mice, relaxation to H2O2 was impaired, but responses to adenosine and acetylcholine were normal compared with those from WT mice. CONCLUSIONS: Kv1.5 channels in vascular smooth muscle play a critical role in coupling myocardial blood flow to cardiac metabolism. Absence of these channels disassociates metabolism from flow, resulting in cardiac pump dysfunction and tissue hypoxia.

Lead Macrodislodgement of a Subcutaneous Implantable Cardioverter-Defibrillator Results in a Reel Problem.

Lead macrodislodgement is a rare complication of cardiac implantable electronic devices associated with patient-related risk factors. This paper outlines a case of reel syndrome secondary to device manipulation 3 months after subcutaneous implantable cardioverter-defibrillator implantation and describes the challenges with lead macrodislodgement diagnosis, mechanisms, and management. (Level of Difficulty: Beginner.).