Background - The inspIRE study evaluated safety and effectiveness of a fully integrated biphasic pulsed field ablation (PFA) system with a variable loop circular catheter for the treatment of drug-refractory paroxysmal atrial fibrillation (AF). Methods - Subjects underwent pulmonary vein isolation (PVI) with the PFA system, using at least 12 applications per vein; adenosine/isoproterenol was administered to confirm entrance block. Wave I assessed initial safety, including for esophageal lesions, silent cerebral lesions (SCLs), and PV stenosis. Wave II (pivotal phase) tested i) primary safety - incidence of early onset primary adverse events (PAEs), and primary effectiveness - confirmed PVI with freedom from documented atrial arrhythmia at 12-months (12M). The study design specified an interim analysis to determine early success once 30 subjects reached 12M follow-up (FU) and all subjects reached 3M FU. Results - Across 13 centers in Europe/Canada, 226 subjects were enrolled, met criteria for safety and effectiveness evaluations and received PFA (Wave I: 40; Wave II: 186). Wave I demonstrated no esophageal thermal lesions or PV stenosis. Among 39 subjects with cerebral MRI, SCLs were detected in 4 of the first 6 subjects, after which workflow enhancements, including a 10s pause between PFA applications was implemented; subsequently, only 4 of 33 subjects had SCLs. In the Wave II phase, no PAE was reported. Upon declaring early success, 83 subjects reached 12M FU. With 100% entrance block, PVI without acute reconnection was achieved in 97.1% of targeted veins. For Wave II, the primary effectiveness endpoint per Kaplan Meier at the time of interim analysis was 70.9%; 12M freedom from symptomatic AF/atrial flutter/atrial tachycardia recurrence and repeat ablation was 78.9% and 92.3%, respectively. Total procedure and transpired PFA times were 70.1 ± 27.7 min and 26.7 ± 14.0 min, respectively. Conclusions - The inspIRE trial confirmed the safety and effectiveness of the novel mapping-integrated PFA system.

Ibrutinib represents the first approved treatment for patients with Waldenström macroglobulinemia (WM). There are very few published experiences outside of a clinical trial. In this study, we investigated treatment response, survival, and safety in a real life setting. We retrospectively analyzed 49 consecutive R/R WM patients, managed in 8 Tuscan onco-hematological centers, that received ibrutinib after its approval, at a maximum dose of 420 mg once per day, until disease progression or unacceptable toxicity. Median age was 65 years (range 32-86), and the median number of previous regimens was 2 (range 1-5). Overall and major response rate were 91.8% and 87.7%, respectively. At best response, median IgM level declined from 3,094 to 831 mg/dl, and Hb level increased from 10.4 to 12.7 g/dl. In an intention-to-treat analysis, 36/49 patients (73.5%) were still receiving treatment, while 13/49 (26.5%) had discontinued therapy. Six out of 49 cases (12.2%) relapsed after an initial response, and 13/49 (26.5%) had a dose reduction. Estimated 2-year PFS, DOR, and OS were 76.7%, 88.7%, and 84.1%, respectively. After a median follow-up of 18.3 months, 43/49 patients (87.8%) were alive. The most frequent AE included atrial fibrillation or flutter (6/49 cases, 12.2%), bleeding (6/49 cases, 12.2%), arthralgia/myalgia (5/49 cases, 10.2%). Ibrutinib is a suitable treatment option for R/R WM patients and also suggested by ESMO, NCCN, and other societies. PFS and OS were durable, and DOR was sustained for responsive patients. Treatment toxicity is not negligible, but manageable in most cases without treatment discontinuation.

An electrocardiogram showing atrial flutter in which varying ratios of AV conduction and the cyclical recurrence of varying QRS morphologies are observed is presented.

We sought to describe the clinical outcomes, resource utilization, and treatment options for patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) over the course of their disease. Adults with obstructive HCM who were symptomatic were identified from the IBM MarketScan Commercial and Medicare supplemental database (January 2009 to March 2019). The index date was the initial obstructive HCM diagnosis date. Patients were required to have ≥12-month continuous eligibility before and after the index date. Incidence rates (IRs) and cumulative risk of cardiovascular events, healthcare resource utilization, and pharmacotherapy were assessed after index and compared with matched controls. Among 4,617 eligible patients with obstructive HCM, 2,917 (63.2%, mean age 60, 47.2% women) were symptomatic at index date. The most common cardiovascular events were atrial fibrillation/flutter (IR:1.421 per person-year [PPY], heart failure (IR: 0.895 PPY), and dyspnea (IR:0.797 PPY). Patients incurred higher resource use with frequent tests and monitoring, hospitalizations (0.454 PPY), and emergency room visits (0.611 PPY). The use of pharmacotherapy increased from 61.2% in the 6-month preindex period to 83.9% in the 6-month postindex period and remained stable after diagnosis. These events ranged from 3 to over 60-fold higher compared with controls, with the largest difference observed in arrhythmic events. The majority of patients were symptomatic at the time of obstructive HCM diagnosis, resulting in significantly increased cardiovascular complications and frequent disease monitoring after diagnosis versus controls. In conclusion, healthcare resource utilization was substantial, and these findings suggest a higher clinical and economic burden over the disease course among patients with symptomatic obstructive HCM, despite current treatment.

Supraventricular tachycardia is a common occurrence in routine clinical practice. As a physician, one can encounter them everywhere, whether as a general practitioner or as an emergency doctor in a hospital. Some tachycardias might have robbed an on-call doctor the night or the last nerve; however, supraventricular tachycardia is usually a benign condition that is easily treatable and, in many cases, even curable. This article covers the differential diagnoses of supraventricular tachycardia and its treatment options. Atrial fibrillation, also a supraventricular tachycardia, is not discussed in this article.

Heart Failure (HF) and Opioid Use Disorder (OUD) independently have significant impact on patients and the United States (US) health system. In the setting of the opioid epidemic, research on the effects of OUD on cardiovascular diseases is rapidly evolving. However, no study exists on differential outcomes of ischemic cardiomyopathy (ICM) and non-ischemic cardiomyopathy (NICM) in patients with HF with OUD. We performed a retrospective, observational cohort study using National Inpatient Sample (NIS) 2018-2020 databases. Patients aged 18 years and above with diagnoses of HF with concomitant OUD were included. Patients were further classified into ICM and NICM. Primary outcome of interest was differences in all- cause in-hospital mortality. Secondary outcome was incidence of cardiogenic shock. We identified 99,810 hospitalizations that met inclusion criteria, ICM accounted for 27%. Mean age for ICM was higher compared to NICM (63 years vs 56 years, p<0.01). Compared to NICM, patients with ICM had higher cardiovascular disease risk factors and comorbidities; type 2 diabetes mellitus (46.3 % vs 30.1%, p<0.01), atrial fibrillation/flutter (33.5% vs 29.9%, p<0.01), hyperlipidemia (52.5% vs 28.9%, p<0.01), and Charlson comorbidity index ≥ 5 was 46.7% vs 29.7%, p<0.01. After controlling for covariates and potential confounders, we observed higher odds of all-cause in-hospital mortality in patients with NICM (aOR=1.36; 95% CI:1.03-1.78, p=0.02). There was no statistical significant difference in incidence of cardiogenic shock between ICM and NICM (aOR=0.86;95% CI 0.70-1.07, p=0.18). In patients with HF with concomitant OUD, we found a 36% increase in odds of all-cause in-hospital mortality in patients with NICM compared to ICM despite being younger in age with less comorbidities. There was no difference in odds of in-hospital cardiogenic shock in this study population. This study contributes to the discussion of OUD and cardiovascular diseases which is rapidly developing and requires further prospective studies.

Quinine is an anti-malarial drug with documented hematologic, dermatologic, and cardiovascular side effects. Tonic water contains a sub-therapeutic amount of quinine and is available over the counter. However, the public is unaware of the risks associated with excessive consumption of tonic water. We present a patient who developed atrial flutter with a rapid ventricular response following the consumption of tonic water. The patient responded to rate control therapy and was discharged the following day with a plan to follow up in the outpatient department with an electrophysiologist. Although quinine has been shown to have ventricular anti-arrhythmic effects, its effect on the atria has not been determined. We present this case to bring greater awareness to the cardiovascular risks associated with the consumption of tonic water to reduce morbidity and mortality.

Cardiovascular disease remains one of the leading causes of death in China, with increasingly serious negative effects on people and society. Despite significant advances in preventing and treating cardiovascular diseases, such as atrial fibrillation/flutter and heart failure over the last few years, much more remains to be done. Therefore, developing innovative methods for identifying and managing cardiovascular disorders is critical. Nanomaterials provide multiple benefits in biomedicine, primarily better catalytic activity, drug loading, targeting, and imaging. Biomimetic materials and nanoparticles are specially combined to synthesize biomimetic nanoparticles that successfully reduce the nanoparticles' toxicity and immunogenicity while enhancing histocompatibility. Additionally, the biological targeting capability of nanoparticles facilitates the diagnosis and therapy of cardiovascular disease. Nowadays, nanomedicine still faces numerous challenges, which necessitates creating nanoparticles that are highly selective, toxic-free, and better clinically applicable. This study reviews the scientific accomplishments in this field over the past few years covering the classification, applications, and prospects of noble metal biomimetic nanozymes and biomimetic nanocarriers.

The association between type 2 diabetes (T2D) and the development of cardiac arrhythmias and conduction disturbances has not been extensively studied. Arrhythmia was defined as atrial fibrillation and flutter (AF/AFl), ventricular tachycardia (VT) and ventricular fibrillation (VF), and conduction abnormality as sinus node disease (SND), atrioventricular (AV) block or pacemaker implantation, and intraventricular conduction blocks (IVCB). Incidence rates and Cox regression were used to compare outcomes, and to assess optimal levels for cardiometabolic risk factors and risk associated with multifactorial risk factor control (i.e., HbA1c, LDL-C, systolic blood pressure (SBP), BMI and eGFR), between patients with versus without T2D. The analyses included data from 617,000 patients with T2D and 2,303,391 matched controls. Patients with diabetes and the general population demonstrated a gradual increase in rates for cardiac conduction abnormalities and virtually all age-groups for AF/AFI showed increased incidence during follow-up. For patients with versus without T2D, risks for cardiac arrhythmias were higher, including for AF/AFl (HR 1.17, 95% CI 1.16-1.18), the composite of SND, AV-block or pacemaker implantation (HR 1.40, 95% CI 1.37-1.43), IVCB (HR 1.23, 95% CI 1.18-1.28) and VT/VF (HR 1.08, 95% CI 1.04-1.13). For patients with T2D who had selected cardiometabolic risk factors within target ranges, compared with controls, risk of arrythmia and conduction abnormalities for T2D vs not were: AF/AFl (HR 1.09, 95% CI 1.05-1.14), the composite of SND, AV-block or pacemaker implantation (HR 1.06, 95% CI 0.94-1.18), IVCB (HR 0.80, 95% CI 0.60-0.98), and for VT/VF (HR 0.97, 95% CI 0.80-1.17). Cox models showed a linear risk increase for SBP and BMI, while eGFR showed a U-shaped association. Individuals with T2D had a higher risk of arrhythmias and conduction abnormalities than controls, but excess risk associated with T2D was virtually not evident among patients with T2D with all risk factors within target range. BMI, SBP and eGFR displayed significant associations with outcomes among patients with T2D.

Tachycardia-induced cardiomyopathy is an entity characterized by reversible dysfunction of the left ventricle, which can be induced by different types of arrhythmia such as atrial fibrillation, atrial flutter, incessant supraventricular tachycardia and ventricular arrhythmia (more frequent causes). Correct identification of the causative arrhythmia and normalization of the heart rate (e.g through medical treatment, electrical cardioversion, ablation) can lead to recovery of left ventricular function. Tachycardia-induced cardiomyopathy should be suspected in patients with tachycardia and left ventricular dysfunction (heart failure setting), especially when there is no history of previous heart disease. Its usual phenotype is that of non-ischaemic/non-valvular dilated cardiomyopathy and it can occur in both children (main cause: permanent junctional reciprocating tachycardia) and adults (main cause: atrial fibrillation). With proper treatment, most cases recover within a few months, though there is a risk of relapse, especially when the causal arrhythmia reappears or its control is lost. This is a narrative review that comprehensively addresses the pathophysiology, clinical manifestations, and therapeutic management of tachycardia-induced cardiomyopathy. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment.

Infantile-onset Pompe disease manifests with early signs of cardiomyopathy during the first few days to weeks of life. We present the case of a newborn born via emergency cesarean section with atrial flutter and moderate biventricular hypertrophy who was diagnosed with Pompe disease on New York State newborn screen. Diagnosis was confirmed with repeat leukocyte acid alpha-glucosidase (GAA) enzyme activity, GAA gene sequencing, urine Hex4, and evaluation of Cross-Reactive Immunological Material (CRIM) status. The patient was also found to be persistently neutropenic which to our knowledge has not been previously reported in the literature in association with Pompe disease. This report highlights the impact that newborn screening had on time to diagnosis and initiation of treatment with enzyme replacement therapy. We also discuss how our patient's concurrent neutropenia impacted decision making related to immune tolerance induction prior to starting enzyme replacement therapy.