The late fifties are considered a high point in the history of cardiac pacing, since this era is marked by the first pacemaker implantation, which has since evolved into life-saving therapy. Right ...ventricular apical and biventricular pacing are the classic techniques that are recommended as first-l ine approaches for most indications in current guidelines. However, conduction system pacing has emerged as being able to deliver a more physiological form of pacing and is becoming mainstream practice in a growing number of centres. In this review, we aim to compare traditional pacing methods with conduction system pacing.
Initial treatment of paroxysmal atrial fibrillation with cryoballoon ablation was associated with a lower incidence of persistent atrial fibrillation and other atrial tachyarrhythmias over 3 years ...than rhythm-control medications.
Empagliflozin (EMPA) reduces heart failure hospitalization and mortality. The benefit in terms of ventricular arrhythmia and contractility has not been explored.
To determine the direct effects of ...EMPA on ventricular arrhythmia and cardiac contractility in an ex-vivo model of global ischemia-reperfusion (I/R).
Langendorff-perfused rabbit hearts were subjected to 30 min of complete perfusion arrest and reperfusion. Either EMPA (1 μM) or normal saline (controls) was then infused into the perfusate in a randomized fashion. Ten minutes following drug infusion, calcium imaging was performed. At the end of each experiment, the heart was electrically stimulated 5 times to assess the inducibility of ventricular fibrillation (VF). In a separate series of experiments, left ventricular (LV) pressure and epicardial NADH fluorescence were simultaneously recorded. LV specimens were then collected for western blotting.
Post-ischemia, EMPA treatment was associated with reduction in the induction of VF >10s (rate of induction: 16.7 ± 3.3% vs. 60 ± 8.7% in control hearts, p = 0.003), improvement of LV developed pressure (LVDP; 68.10 ± 9.02% vs. 47.61 ± 5.15% in controls, p = 0.03) and reduction of NADH fluorescence (87.42 ± 2.79% vs. 112.88 ± 2.27% in control hearts, p = 0.04) along with an increase in NAD+/NADH ratio (2.75 ± 0.55 vs. 1.09 ± 0.32 in the control group, p = 0.04) A higher calcium amplitude alternans threshold was also observed with EMPA-treatment (5.42 ± 0.1 Hz vs. 4.75 ± 0.1 Hz in controls, p = 0.006). Sodium-glucose co-transporter-2 (SGLT2) expression was not detected in LV tissues.
EMPA treatment reduced ventricular arrhythmia vulnerability and mitigated contractile dysfunction in the global I/R model while improving calcium cycling and mitochondrial redox by SGLT2-independent mechanisms.
In normoxic conditions, NADH is generated by the reduction of NAD+ in metabolic pathways by glucose oxidation and Krebs cycle. NADH is oxidized to NAD+ by ETC to produce ATP. ETC dysfunction during hypoxia (Red dotted arrow) is associated with the accumulation of NADH. Improvement of ETC function by EMPA (Blue solid arrow) leads to increase in NAD+/NADH ratio, improvement of contractile function, improvement of cytosolic calcium dynamics, and reduction of vulnerability to ventricular arrhythmias.
Glu: Glucose, Pyr: Pyruvate, TCA cycle: Tricarboxylic acid cycle (Krebs cycle), ETC: Electron transport chain, EMPA: Empagliflozin, I/R: Ischemia-reperfusion, SR: Sarcoplasmic reticulum. Display omitted
•Cardioprotective effects of Empagliflozin were evaluated in a model of global ischemia-reperfusion (I/R)•Empagliflozin increased contractility and decreased ventricular arrhythmia vulnerability•Improvements in mitochondrial redox state and cytosolic calcium dynamics were also noted with Empagliflozin treatment•In our Langendorff model, the cardioprotective effects of Empagliflozin were independent of SGLT2 inhibitory actions•These cardioprotective actions may explain the favorable effects of SGLT2i agents in heart failure which is independent of blood sugar control
In this multicenter trial involving patients with paroxysmal atrial fibrillation who had not previously received rhythm-control treatment, cryoballoon ablation resulted in a significantly higher ...percentage of patients with treatment success at 1 year than antiarrhythmic drug therapy, with a low incidence of procedure-related adverse events.
Amiodarone is an iodinated benzofuran derivative, a highly lipophilic drug with unpredictable pharmacokinetics. Although originally classified as a class III agent due to its ability to prolong ...refractoriness in cardiac regions and prevent/terminate re-entry, amiodarone shows antiarrhythmic properties of all four antiarrhythmic drug classes. Amiodarone is a potent coronary and peripheral vasodilator, can be safely used in patients with left ventricular dysfunction after myocardial infarction or those with congestive heart failure or hypertrophic cardiomyopathy, and is rarely associated with QT interval prolongation and ventricular pro-arrhythmia. It is the most powerful pharmacological agent for long-term sinus rhythm maintenance in patients with atrial fibrillation. Amiodarone, particularly if co-administered with beta-blockers, reduces the rate of arrhythmic death due to ventricular tachyarrhythmias in patients with heart failure, but its benefit on cardiovascular and overall survival in these patients is uncertain. In addition, amiodarone is an important adjuvant drug for the reduction of shocks in patients with an implantable cardioverter-defibrillator. Due to its beneficial pharmacological profile amiodarone became the most prescribed antiarrhythmic drug over the past 40 years. Nevertheless, the slow onset of its antiarrhythmic action requires a loading dose and the high risk of non-cardiac toxicity and common drug-drug interactions limit its long-term use. Therefore amiodarone is generally considered a secondary therapeutic option, particularly if alternative antiarrhythmic strategies are not available or are not indicated. Long-term treatment with amiodarone should be based on the use of minimal doses for satisfactory arrhythmia outcome and serial screening for thyroid, liver and pulmonary toxicity.
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Amiodarone is an iodinated benzofuran derivative, a highly lipophilic drug with unpredictable pharmacokinetics. Although originally classified as a class III agent due to its ability to prolong refractoriness in cardiac regions and prevent/terminate re-entry, amiodarone shows antiarrhythmic properties of all four antiarrhythmic drug classes. Amiodarone is a potent coronary and peripheral vasodilator and can be safely used in patients with left ventricular dysfunction after myocardial infarction or those with congestive heart failure or hypertrophic cardiomyopathy. Its use is regularly accompanied with QT and QTc-interval prolongation but rarely with ventricular proarrhythmia. It is the most powerful pharmacological agent for long-term sinus rhythm maintenance in patients with atrial fibrillation. Amiodarone, particularly if co-administered with beta-blockers, reduces the rate of arrhythmic death due to ventricular tachyarrhythmias in patients with heart failure, but its benefit on cardiovascular and overall survival in these patients is uncertain. In addition, amiodarone is an important adjuvant drug for the reduction of shocks in patients with an implantable cardioverter-defibrillator. Over the past 40 years, amiodarone became the most prescribed antiarrhythmic. Nevertheless, the slow onset of its antiarrhythmic action requires a loading dose while the high risk of non-cardiac toxicity and common drug-drug interactions limit its long-term use. Furthermore patients treated with amiodarone require a close supervision by the treating physician. Therefore amiodarone is generally considered a secondary therapeutic option. Long-term treatment with amiodarone should be based on the use of minimal doses for satisfactory arrhythmia outcome and serial screening for thyroid, liver and pulmonary toxicity.
The short QT syndrome (SQTS) is an inherited arrhythmogenic syndrome characterized by abnormal ion channel function, life-threatening arrhythmias, and sudden cardiac death.
The purpose of this study ...was to establish a patient-specific human-induced pluripotent stem cell (hiPSC) model of the SQTS, and to provide mechanistic insights into its pathophysiology and therapy.
Patient-specific hiPSCs were generated from a symptomatic SQTS patient carrying the N588K mutation in the KCNH2 gene, differentiated into cardiomyocytes, and compared with healthy and isogenic (established by CRISPR/Cas9-based mutation correction) control hiPSC-derived cardiomyocytes (hiPSC-CMs). Patch-clamp was used to evaluate action-potential (AP) and IKr current properties at the cellular level. Conduction and arrhythmogenesis were studied at the tissue level using confluent 2-dimensional hiPSC-derived cardiac cell sheets (hiPSC-CCSs) and optical mapping.
Intracellular recordings demonstrated shortened action-potential duration (APD) and abbreviated refractory period in the SQTS-hiPSC-CMs. Similarly, voltage- and AP-clamp recordings revealed increased IKr current density due to attenuated inactivation, primarily in the AP plateau phase. Optical mapping of the SQTS-hiPSC-CCSs revealed shortened APD, impaired APD-rate adaptation, abbreviated wavelength of excitation, and increased inducibility of sustained spiral waves. Phase-mapping analysis revealed accelerated and stabilized rotors manifested by increased rotor rotation frequency, increased rotor curvature, decreased core meandering, and increased rotor complexity. Application of quinidine and disopyramide, but not sotalol, normalized APD and suppressed arrhythmia induction.
A novel hiPSC-based model of the SQTS was established at both the cellular and tissue levels. This model recapitulated the disease phenotype in the culture dish and provided important mechanistic insights into arrhythmia mechanisms in the SQTS and its treatment.
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Remarkable progress has been made in the development of new therapies for cancer, dramatically changing the landscape of treatment approaches for several malignancies and continuing to increase ...patient survival. Accordingly, adverse effects of cancer therapies that interfere with the continuation of best-possible care, induce life-threatening risks or lead to long-term morbidity are gaining increasing importance. Cardiovascular toxic effects of cancer therapeutics and radiation therapy are the epitome of such concerns, and proper knowledge, interpretation and management are needed and have to be placed within the context of the overall care of individual patients with cancer. Furthermore, the cardiotoxicity spectrum has broadened to include myocarditis with immune checkpoint inhibitors and cardiac dysfunction in the setting of cytokine release syndrome with chimeric antigen receptor T cell therapy. An increase in the incidence of arrhythmias related to inflammation such as atrial fibrillation can also be expected, in addition to the broadening set of cancer therapeutics that can induce prolongation of the corrected QT interval. Therefore, cardiologists of today have to be familiar not only with the cardiotoxicity associated with traditional cancer therapies, such as anthracycline, trastuzumab or radiation therapy, but even more so with an ever-increasing repertoire of therapeutics. This Review provides this information, summarizing the latest developments at the juncture of cardiology, oncology and haematology.
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