Background: Estimating contractility of the left ventricle with noninvasive techniques is an important yet elusive goal. Positive inotropic interventions are mirrored by smaller end-systolic volumes and higher end-systolic pressures. An increased heart rate progressively increases the force of ventricular contraction (Bowditch treppe or staircase phenomenon). Aim: To assess the feasibility of a noninvasive estimation of force−frequency relation (FFR) during pacing stress in the echo lab in patients with permanent pacemaker (PM). Methods: Transthoracic stress pacing echocardiography was performed in 26 patients with a permanent pacemaker (age 69±11 years; 21 men, 5 women). Seven patients had normal function at baseline and during stress (“normals”); eight had angiographically assessed coronary artery disease (three with and five without induced ischemia with stress echo); eleven patients had dilated cardiomyopathy (DC). To build the FFR, the force was determined at different steps as the ratio of the systolic pressure (SP, cuff sphygmomanometer)/end-systolic volume index (ESV, biplane Simpson rule/body surface area). Heart rate was determined from ECG. Results: The absolute value of the FFR slope was highest in controls and lowest in DC patients. A flat-downsloping FFR was found in 12/19 patients but not for normals (p<0.01). Conclusions: Noninvasive pacemaker stress echocardiography (PASE) is a simple and efficient option to assess left ventricular (LV) contractility in patients with permanent pacemaker.

Background and Purpose: Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with an increased risk for stroke, heart failure and cardiovascular‐related mortality. Candidate targets for anti‐AF drugs include a potassium channel K_v1.5, and the ionic currents I_KACh and late I_Na, along with increased oxidative stress and activation of NFAT‐mediated gene transcription. As pharmacological management of AF is currently suboptimal, we have designed and characterized a multifunctional small molecule, compound 1 (C1), to target these ion channels and pathways.Experimental Approach: We made whole‐cell patch‐clamp recordings of recombinant ion channels, human atrial I_Kur, rat atrial I_KACh, cellular recordings of contractility and calcium transient measurements in tsA201 cells, human atrial samples and rat myocytes. We also used a model of inducible AF in dogs.Key Results: C1 inhibited human peak and late K_v1.5 currents, frequency‐dependently, with IC₅₀ of 0.36 and 0.11 μmol·L⁻¹ respectively. C1 inhibited I_KACh (IC₅₀ of 1.9 μmol·L⁻¹) and the Na_v1.5 sodium channel current (IC₅₀s of 3 and 1 μmol·L⁻¹ for peak and late components respectively). C1 (1 μmol·L⁻¹) significantly delayed contractile and calcium dysfunction in rat ventricular myocytes treated with 3 nmol·L⁻¹ sea anemone toxin (ATX‐II). C1 weakly inhibited the hERG channel and maintained antioxidant and NFAT‐inhibitory properties comparable to the parent molecule, resveratrol. In a model of inducible AF in conscious dogs, C1 (1 mg·kg⁻¹) reduced the average and total AF duration.Conclusion and Implications: C1 behaved as a promising multifunctional small molecule targeting a number of key pathways involved in AF.

Introduction: Routine ultrasound (US) guidance for femoral venous access to decrease vascular complications of atrial fibrillation (AF) ablation procedures has been advocated. However, the benefit has not been unequivocally demonstrated by randomized‐trial data.Methods: Consecutive patients undergoing pulmonary vein isolation (PVI) on uninterrupted anticoagulant treatment were included. A quasi‐random allocation to either US‐guided or conventional puncture group was based on which of the two procedure rooms the patient was scheduled in, with only one of the rooms equipped with a US machine including a vascular transducer. The same four novice operators in rotation, with no relevant previous experience in US‐guided vascular access performed venous punctures in both rooms. Major and minor vascular complications and the rate of prolonged hospitalization were compared. Major vascular complication was defined as groin hematoma, arteriovenous fistula, or pseudoaneurysm. Hematoma was considered as a major vascular complication if it met type 2 or higher Bleeding Academic Research Consortium criteria (requiring nonsurgical, medical intervention by a health care professional; leading to hospitalization or increased level of care, or prompting evacuation).Results: Of the 457 patients 199 were allocated to the US‐guided puncture group, while the conventional, palpation‐based approach was performed in 258 cases. Compared with the conventional technique, US guidance reduced the rate of any vascular complication (11.63% vs. 2.01%, p < .0001), including both major (4.26% vs. 1.01%, p = .038) and minor (7.36% vs. 1.01%, p = .001) vascular complications. In addition, the rate of prolonged hospitalization was lower in the US‐guided puncture group (5.04% vs. 1.01%, p = .032).Conclusion: The use of US for femoral vein puncture in patients undergoing PVI decreased the rate of both major and minor vascular complications. This quasi‐randomized comparison strongly supports adapting routine use of US for AF ablation procedures.