Ischemic Arrhythmias Research Articles

Cardioprotective Effect of Chronic Hypoxia Involves Inhibition of Mitochondrial Permeability Transition Pore Opening

The aim of the study was to examine the potential role of mitochondrial permeability transition pore (mPTP) in the cardioprotective effect of chronic continuous hypoxia (CH) against acute myocardial ischemia/reperfusion (I/R) injury. Adult male Wistar rats were adapted to CH for 3 weeks, while their controls were kept under normoxic conditions. Subsequently, they were subjected to I/R insult while being administered with mPTP inhibitor, cyclosporin A (CsA). Infarct size and incidence of ischemic and reperfusion arrhythmias were determined. Our results showed that adaptation to CH as well as CsA administration reduced myocardial infarct size in comparison to the corresponding control groups. However, administration of CsA did not amplify the beneficial effect of CH, suggesting that inhibition of mPTP opening contributes to the protective character of CH.

Increased risk of cardiovascular events in the weeks following hospitalised COPD exacerbations: the EXACOS-CV French nationwide case-crossover study

Abstract Introduction Previous studies indicate that in people living with chronic obstructive pulmonary disease (COPD), the risk of myocardial infarction (MI), heart failure (HF) decompensation, arrhythmias and ischemic stroke increases following a COPD exacerbation. This association has not been explored for detailed types of cardiovascular events (CVE), namely for different types of myocardial infarction. Objective To quantify the risk of CVE following a COPD exacerbation overall, and by detailed type of CVE. Methods A case-crossover study was conducted using the French national hospital discharge database (Programme de Médicalisation des Systèmes d'Information, PMSI). Case-patients: (i) were aged≥40 years with a COPD diagnosis; (ii) hospitalised in 2018-2019 for CVE; (iii) experienced the CVE within 24 weeks of a hospitalised exacerbation of COPD. Hospitalisation date for CVE was index date. Conditional logistic regression models estimated the association between a hospitalised exacerbation and CVE (overall and by type of CVE) – expressed as odds ratios (OR) – comparing the odds of a hospitalised COPD exacerbation during the risk period (4 weeks prior to index date) versus control periods (9-24 weeks prior to index date). Results Among 122,172 patients with COPD hospitalised for a severe CVE in 2018-2019, 9,840 (8%) had a hospitalised exacerbation of COPD in the prior 24 weeks and qualified as case-patients. Mean age was 76.8 years (SD 10.7); 6,496 (66%) were male. The most frequent CVE were decompensated heart failure (n=5,888, 60%) and acute coronary syndrome (n=1,070, 11%); in-hospital death in the 24 weeks following an exacerbation of COPD occurred in 950 (10%) patients. Median time elapsed between hospitalised exacerbation and CVE (any type) was 43 days (Figure 1); the shortest delays were observed for non-STEMI (24 days) and resuscitated cardiac arrest (28 days). Risk of CVE in the 4 weeks following a hospitalised COPD exacerbation was 3-times the risk in the 9-24 weeks post-exacerbation (OR 3.0; 95%CI 2.9-3.2 – Figure 2). This increase in risk was observed for each individual type of CVE. The highest effect size was observed for non-STEMI (OR 5.3; 95%CI 4.5-6.3). Conclusion The risk of CVE substantially increases following a hospitalised exacerbation of COPD overall and for all types of CVE (acute ischemic events, arrhythmias, and heart failure decompensation). The first month following a hospitalised exacerbation is a period of vulnerability for people living with COPD, with some variability in the magnitude and temporality of risk increase according to the type of CVE. These results stress the need for immediate and sustained monitoring of exacerbating COPD patients to prevent a subsequent severe cardiac event. In addition, exacerbations prevention is an essential target of COPD treatment.

Cardiac Failure and Cardiogenic Shock: Insights Into Pathophysiology, Classification, and Hemodynamic Assessment.

Heart failure is defined as increased intracardiac pressures, either alone or combined with reduced cardiac output. Clinically, it is presented with signs and symptoms of congestion and compensated perfusion. Cardiogenic shock, on the other hand, is the spectrum of hemodynamic disturbances that lead to hypoperfusion or need for circulatory support, due to cardiac disease. Both entities affect millions of people worldwide, have a dismal prognosis, and constitute a severe socioeconomic burden. Heart failure can be the aftermath of ischemic heart disease, hypertension, arrhythmias, or cardiomyopathies. It undergoes multiple classifications, facilitating its investigation and treatment. The pathogenetic mechanisms differ in various types of heart failure, regarding the affected ventricles, the duration of symptoms, and their primary/secondary onset. These mechanisms reflect the complex interactions between cardiopulmonary, vascular, and hepatorenal systems. Acute deterioration of cardiac function can lead to cardiogenic shock. Myocardial infarction accounts for 81% of such cases. Healthy lifestyle and timely management of coronary artery disease are paramount, as they can prevent this life-threatening situation and reduce mortality and the economic burden for healthcare systems. Irrespective of the etiology, cardiogenic shock is interpreted using the pressure-volume loop. This can be modified for each ventricle, the underlying pathophysiology, and the time since symptoms' onset. It therefore provides valuable information about the native circulation and the expected alterations under mechanical or pharmacological support, facilitating the decision-making progress. In 2019, given the phenotypical heterogeneity of cardiogenic shock, the Society for Cardiovascular Angiography and Interventions introduced a classification system. According to this, patients are stratified in five stages proportionally to the severity of their condition. Aside from this classification, various biochemical, imaging, and hemodynamic monitoring indices are used to assess coagulation pathway and cardiac, hepatorenal, and pulmonary function, enabling the heart team to tailor therapy. Additionally, the prognostication progress is facilitated by scores, such as the Observatoire Regional Breton sur l'Infarctus (ORBI) score, the intra-aortic balloon pump (IABP) SHOCK-II score, and the CardShock score, indicating suitable escalation or de-escalation strategies. Despite the current progress, there are several areas of advancement regarding the role of vasoactive drugs in cardiogenic shock, revascularization options, mechanical ventilation patterns, hypothermia treatment, and mechanical circulatory support protocols.

Major Adverse Cardiovascular Events Following Coronary Artery Stenting by History of Hypertensive Disorder of Pregnancy.

A history of hypertensive disorders of pregnancy is associated with at least twice the risk of incident ischemic heart disease. Whether the long-term outcome following treatment with coronary artery stenting is associated to the history of hypertensive disorders of pregnancy is unknown. We included 8364 women (age ≤65 years) undergoing first coronary artery stenting 2006 to 2022 following their first delivery in 1973 or later, linking nationwide data on percutaneous coronary intervention and delivery history. In total, 1122 women (13.4%) had a history of hypertensive disorders of pregnancy. The main outcome, a major adverse cardiovascular event, was defined as any incident myocardial infarction, ischemic heart disease, cardiac arrest, arrhythmias, angina pectoris, heart failure, cerebral infarction, or sudden death. During a median follow-up time of 5 years, 258 women with a history of hypertensive disorders of pregnancy had a major adverse cardiovascular event, compared with 1465 women without a history of hypertensive disorders of pregnancy (23% versus 20.2%, P=0.028 for log-rank test). Estimates adjusted for patient- and procedural characteristics in proportional hazards regression models suggested that the hazard rate increased only after 4-8 years of follow-up (hazard ratio [HR], 1.36 [95% CI, 1.05-1.78]) and was primarily driven by women with history of gestational hypertension (HR, 2.15 [95% CI, 1.49-3.11]). Women with a history of hypertensive disorders of pregnancy have an increased risk of a major adverse cardiovascular event following coronary artery stenting compared with other parous women. A history of hypertensive disorders of pregnancy warrants further attention in the secondary prevention setting of coronary artery disease.

A light-addressable potentiometric sensor-based extracellular calcium dynamic monitoring and imaging platform for cellular calcium channel drug evaluation

Disruption and dysregulation of cellular calcium channel function can lead to diseases such as ischemic stroke, heart failure, and arrhythmias. Corresponding calcium channel drugs typically require preliminary efficacy evaluations using in vitro models such as cells and simulated tissues before clinical testing. However, traditional detection and evaluation methods often encounter challenges in long-term continuous monitoring and lack calcium specificity. In this study, a dynamic monitoring system based on ion-sensitive membranes for light-addressable potentiometric sensor (LAPS) was developed to meet the demand for monitoring changes in extracellular calcium ion (Ca2+) concentration in live cells. The effects of Ca2+ channel agonists and blockers on 2D and 3D HL-1 cells were investigated, with changes in extracellular Ca2+ concentration reflecting cellular calcium metabolism, facilitating drug evaluation. Additionally, calcium imaging technology with optical addressing capability complemented the LAPS system's ability to perceive 3D cell morphology, enhancing its drug evaluation capabilities. This work provides a novel, label-free, specific, and stable technique for monitoring cellular calcium metabolism. It achieves both continuous monitoring at single points and custom sensing area calcium imaging, holding significant implications for drug screening and disease treatment related to human calcium homeostasis.

Neurological and cardiopulmonary manifestations of pulmonary arteriovenous malformations.

Pulmonary arteriovenous malformations (PAVMs) are direct pulmonary artery-to-vein connections without pulmonary capillaries that result in intrapulmonary right-to-left blood shunts. Although most patients with PAVMs may be entirely asymptomatic, PAVMs can induce a series of complications involving the neurological, cardiovascular, and respiratory systems that can lead to catastrophic and often fatal clinical sequelae. In this study we review the available literature and summarize the reported PAVM-related complications among patients with PAVMs. The reviewed studies included observational studies, case studies, prospective studies, and cohort studies, and we provide an overview of PAVM-related neurological and cardiopulmonary manifestations, including stroke, cerebral abscess, transient ischemic attack, cerebral hemorrhage, migraine, seizure, dizziness, cardiac failure, arrhythmia, myocardial infarction, cough, hypoxemia, dyspnea, respiratory failure, hemoptysis, and hemothorax. Identifying and treating PAVMs before the presentation of major complication is important because this can prevent the occurrence of complications and can result in better outcomes. PAVM patients should thus be better evaluated and managed by a multidisciplinary team because they may be in a treatable phase prior to their condition becoming life-threatening.

Increased risk of major adverse cardiovascular events in young and middle-aged adults with obesity receiving Chinese herbal medicine: A nationwide cohort study.

Many patients with obesity in Taiwan seek Chinese herbal medicines (CHM) from traditional Chinese medicine (TCM) clinics. This study aimed to estimate the risk of major adverse cardiovascular events (MACEs) in adults diagnosed with obesity, with or without CHM. Patients with obesity aged 18 to 50 years were identified using diagnostic codes from Taiwan's National Health Insurance Research Database between 2008 and 2018. We randomized 67,655 patients with or without CHM using propensity score matching. All patients were followed up from the start of the study until MACEs, death, or the end of 2018. A Cox proportional regression model was used to evaluate the hazard ratios of MACEs in the CHM and non-CHM cohorts. During a median follow-up of 4.2 years, the CHM group had a higher incidence of MACEs than the non-CHM control cohort (9.35 versus 8.27 per 1,000 person-years). The CHM group had a 1.13-fold higher risk of MACEs compared with the non-CHM control (adjusted hazard ratio [aHR] = 1.13; 95% confidence interval [CI]: 1.07-1.19; p <0.001), especially in ischemic stroke (aHR = 1.18; 95% CI: 1.07-1.31; p <0.01), arrhythmia (aHR = 1.26; 95% CI: 1.14-1.38; p <0.001), and young adults aged 18 to 29 years (aHR = 1.22; 95% CI: 1.05-1.43; p <0.001). Although certain CHMs offer cardiovascular benefits, young and middle-aged obese adults receiving CHM exhibit a higher risk of MACEs than those not receiving CHM. Therefore, TCM practitioners should be cautious when prescribing medications to young patients with obesity, considering their potential cardiovascular risks.

The Efficacy of Vitamins in the Prevention and Treatment of Cardiovascular Disease.

Vitamins are known to affect the regulation of several biochemical and metabolic pathways that influence cellular function. Adequate amounts of both hydrophilic and lipophilic vitamins are required for maintaining normal cardiac and vascular function, but their deficiencies can contribute to cardiovascular abnormalities. In this regard, a deficiency in the lipophilic vitamins, such as vitamins A, D, and E, as well as in the hydrophilic vitamins, such as vitamin C and B, has been associated with suboptimal cardiovascular function, whereas additional intakes have been suggested to reduce the risk of atherosclerosis, hypertension, ischemic heart disease, arrhythmias, and heart failure. Here, we have attempted to describe the association between low vitamin status and cardiovascular disease, and to offer a discussion on the efficacy of vitamins. While there are inconsistencies in the impact of a deficiency in vitamins on the development of cardiovascular disease and the benefits associated with supplementation, this review proposes that specific vitamins may contribute to the prevention of cardiovascular disease in individuals at risk rather than serve as an adjunct therapy.

O68 ATRIAL SEPTAL ANEURYSM IN IDENTICALS TWINS

Introduction: Interatrial septal aneurysm (ISA) is a dilatation of saccular tissue, generally located in the foramen ovale area, which moves freely and protrudes into the right or left atrium, or even both. Today it is estimated that 85% of children born with congenital heart disease survive to adulthood, however, we have not found cases of ISA reported in identical twins in adulthood. Methods: Two 55-year-old female patients, identical twins EAM and RAM, body surface area 1,899 and 1,826 m2 respectively, consulted for elevated blood pressure (160/90 and 160/95 mmHg respectively). One of them reported headache accompanied by joint pain and mild dyspnea, the other patient reported palpitations and mild dizziness. His parents are hypertensive. They were hospitalized at 5 months of age due to viral meningitis, with no further consequences. Antihypertensive treatment, laboratory, stress test, and echocardiogram/Doppler were prescribed. Results: Laboratory tests were found to be normal. The stress test (protocol: Bruce) was reported to be negative for induced myocardial ischemia. Echocardiography revealed ISA in both patients. Conclusions: Twins, particularly monochorionic twins, are at increased risk of congenital anomalies compared with singleton pregnancies, and the risk of cerebrovascular disease (CVD) or transient ischemic attack (TIA) in patients with ISA is 6.7% in adult patients. ISA has been associated with acquired cardiac diseases, such as valvular heart disease, cardiomyopathies, pulmonary and systemic hypertension, ischemic heart disease, arrhythmias, and thrombus formation. More recently, an association with embolic cerebrovascular pathology has been observed, both in TIA and CVD. For this reason, we consider that in adult patients who are identical twins when one of them is found with ISA, an evaluation should be carried out in their twin for its appropriate treatment and thus avoid future cardiovascular complications derived from this anomaly. According to our reviews, this is the first case of ISA in identical twins. New observations on ISA in twins are needed.

Long-term safety and efficacy of glucagon-like peptide-1 receptor agonists in individuals with obesity and without type 2 diabetes: A global retrospective cohort study.

We aimed to investigate the long-term impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP-1 RA treatment and those who did not receive glucose-lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. After propensity score matching, the study included 12,123 individuals in each group. GLP-1 RA treatment was associated with a significantly lower risk of all-cause mortality (hazard ratio 0.23; 95% confidence interval 0.15-0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP-1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. In this large observational study, GLP-1 RAs showed long-term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP-1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population.

Heat vulnerability: health impacts of heat on older people in urban and rural areas in Europe.

Exposure to extreme heat is associated with both increased morbidity and mortality, especially in older people. Health burdens associated with heat include heat stroke, diabetes mellitus, hypertension, ischemic heart diseases, heart failure and arrhythmia, pulmonary diseases but also injuries, problems with activities of daily living, and mental disorders. In Europe, there are remarkable spatial differences in heat exposure between urban and less populated areas. In Austria, for example, there is asignificant gradual association between population density and the number of heat days, where the gradient of urbanization also follows the gradient of sea level. The European population is continuously ageing, especially in rural areas. Older adults are especially vulnerable to negative health consequences resulting from heat exposure, due to a lack of physiological, social, cognitive, and behavioral resources. Older people living in urban areas are particularly at risk, due to the urban heat island effect, the heat-promoting interplay between conditions typically found in cities, such as alack of vegetation combined with ahigh proportion of built-up areas; however, older people living in rural regions often have less infrastructure to cope with extreme heat, such as fewer cooling centers and emergency services. Additionally, older adults still engaged in agricultural or forestry activities may be exposed to high temperatures without adequate protection or hydration. More research is required to examine factors responsible for heat vulnerability in older adults and the interactions and possibilities for increasing resilience in older urban and rural populations to the health consequences of heat.

Causes and predictors of recurrent unplanned hospital admissions in heart failure patients: a cohort study

Despite progress in therapy, heart failure (HF) inflicts a heavy burden of hospital admissions. In this study, we identified among 1360 community-dwelling HF patients (mean age 70.7 ± 11.3 years, 72.5% men) subgroups sharing similar profiles of unplanned hospital admissions, based on the admission causes and frequency of each cause. Hospital discharge summaries were reviewed for the main admission cause. Patient subgroups were identified via cluster analysis. We investigated baseline predictors associated with these subgroups, using multinomial logistic models. During 3421 patient-years, there were 5192 hospital admissions, of which 4252 (82%) were unplanned. We identified five patient subgroups (clusters 1–5) with distinctive hospitalization profiles. HF accounted for approximately one-third of admissions in the first patient cluster (23% of the patient sample). In contrast, patients in the second cluster (39% of the patient sample) were hospitalized for various reasons, with no single prominent admission cause identified. The other three clusters, comprising 16% of the patient sample, accounted for 42% of all unplanned hospitalizations. While patients in the third cluster were hospitalized mainly due to ischemic heart disease and arrhythmia, patients in the fourth and fifth clusters shared a high burden of recurrent HF admissions. The five patient clusters differed by baseline predictors, including age, functional capacity, comorbidity burden, hemoglobin, and cause of HF. HF patients differ significantly in the causes and overall burden of unplanned hospitalizations. The patient subgroups identified and predictors for these subgroups may guide personalized interventions to reduce the burden of unplanned hospitalizations among HF patients. Trial registration: ClinicalTrials.gov, NCT00533013. Registered 20 September 2007. https://clinicaltrials.gov/study/NCT00533013.

A simulation study on the antiarrhythmic mechanisms of established agents in myocardial ischemia and infarction.

Patients with myocardial ischemia and infarction are at increased risk of arrhythmias, which in turn, can exacerbate the overall risk of mortality. Despite the observed reduction in recurrent arrhythmias through antiarrhythmic drug therapy, the precise mechanisms underlying their effectiveness in treating ischemic heart disease remain unclear. Moreover, there is a lack of specialized drugs designed explicitly for the treatment of myocardial ischemic arrhythmia. This study employs an electrophysiological simulation approach to investigate the potential antiarrhythmic effects and underlying mechanisms of various pharmacological agents in the context of ischemia and myocardial infarction (MI). Based on physiological experimental data, computational models are developed to simulate the effects of a series of pharmacological agents (amiodarone, telmisartan, E-4031, chromanol 293B, and glibenclamide) on cellular electrophysiology and utilized to further evaluate their antiarrhythmic effectiveness during ischemia. On 2D and 3D tissues with multiple pathological conditions, the simulation results indicate that the antiarrhythmic effect of glibenclamide is primarily attributed to the suppression of efflux of potassium ion to facilitate the restitution of [K+]o, as opposed to recovery of IKATP during myocardial ischemia. This discovery implies that, during acute cardiac ischemia, pro-arrhythmogenic alterations in cardiac tissue's excitability and conduction properties are more significantly influenced by electrophysiological changes in the depolarization rate, as opposed to variations in the action potential duration (APD). These findings offer specific insights into potentially effective targets for investigating ischemic arrhythmias, providing significant guidance for clinical interventions in acute coronary syndrome.

Cardiovascular toxicity of fluoropyrimidines: Experience from a quaternary referral center.

e24028 Background: Fluoropyrimidines, including 5-fluorouracil (5-FU) and capecitabine, are widely used chemotherapeutic agents. Their use has been linked to various forms of cardiovascular (CV) toxicity. We sought to analyze the rate of CV events and associated factors in patients receiving fluoropyrimidines at our institution. Methods: We included all patients who received intravenous 5-FU or oral capecitabine at the Cleveland Clinic since 2000. Diagnosis data was obtained based on ICD-10 Codes. CV events included chest pain/angina, myocardial infarction, chronic ischemic heart disease, arrhythmias, conduction disorders, cardiac arrest, cardiomyopathy, and heart failure. CV events were accounted for if they occurred during treatment or within 30 days following the latest administration of the agent. Logistic regression was performed to identify predictors of CV events. Results: A total of 17,236 patients were included, of which 9,386 (54.5) received 5-FU and 7,850 (45.5) received capecitabine. Median age at treatment was 63. The most frequent malignancies were gastrointestinal (70%) and breast cancer (12.3%). A total of 2,283 patients (13.2%) experienced at least one CV event either during treatment or within 30 days following drug administration. The most frequent CV events were chest pain/angina (35.7% of all events). On multivariable logistic regression, factors associated with increased risk of CV events were black race, smoking history, hypertension, and obesity (Table). A prior history of CV disease was also associated with increased risk of CV events (OR 1.22; 95% CI [1.09 - 1.33]). Finally, intravenous 5-FU was linked to higher odds of CV events compared to oral capecitabine (OR 1.48; 95% CI [1.34 - 1.63]). Conclusions: This large-scale cohort study provides pivotal insights into the cardiovascular risks associated with fluoropyrimidine therapy. Besides traditional risk factors, black patients were more likely to suffer from CV events. Additionally, capecitabine may offer better CV outcomes compared to 5-FU. These findings underscore the need for refined risk assessment and enhanced cardiovascular monitoring in patients treated with fluoropyrimidines. [Table: see text]

Patients with bronchiectasis have a lower combined risk of cardiovascular risk factors and cardiovascular comorbidity compared to patients with COPD

Introduction and objectivesChronic respiratory diseases are associated with an increased risk of cardiovascular diseases (CVD); however, it is unknown whether some respiratory diseases are at higher risk than others. In this perspective, head-to-head studies comparing bronchiectasis and chronic obstructive pulmonary disease (COPD) are encouraged. We explored whether the prevalence of cardiovascular risk factors (diabetes mellitus and hyperlipidemia) and cardiovascular comorbidity (systemic hypertension, ischemic heart diseases, cardiac arrhythmia, stroke) are different in these two diseases. MethodsThe present retrospective case-control study aimed to compare patients with bronchiectasis with age and sex-matched individuals with COPD. A total of 63 patients with bronchiectasis and 63 with COPD were retained for analysis. ResultsPatients with bronchiectasis had a lower risk of systemic hypertension (OR 0.42 (C.I. 0.20 to 0.87)) and diabetes mellitus (OR 0.28 (C.I. 0.09 to 0.81)). In contrast, ischemic heart diseases, cardiac arrhythmia, stroke, and hyperlipidemia did not differ between the two groups. Logistic regression analysis showed that age, male sex, and COPD remain independent risk factors for having at least one condition of a composite index including the above-mentioned CVD and CV risk factors. In detail, a patient with COPD has a risk of 4.648 times (C.I. 1.48 to 15.78) for having at least one CVD compared with a patient with bronchiectasis. ConclusionsThe current findings suggest that subjects with bronchiectasis may experience lower cardiovascular risk than those with COPD. Larger studies are needed to confirm this preliminary observation and its clinical implications.

Cryoablation of ventricular tachycardia using ultra-low temperature technology: acute success and insights from the post-interventional CMR

Abstract Background Radiofrequency catheter ablation (RFCA) has good acute and long-term success rates in idiopathic and ischemic ventricular arrhythmia (VA). Drawbacks of the RFCA are reversibility of the edema and limited penetration of the RF energy into the tissue which explain a worse effectiveness in midmyocardial substrates. In comparison to RFCA, the lesions produced by ultra-low temperature cryoablation (ULTC) which uses near-critical nitrogen cryogen at -1960C can be both deeper and irreversible, depending on the duration of the freeze. Purpose We aimed to evaluate the acute effectiveness of a new ULTC technology for VA by examining post-interventional cardiac magnetic resonance images (CMR) with late gadolinium enhancement (LGE), as a part of multi-center Cryocure-VT study. Methods Between December 2022 and May 2023, we ablated 6 patients (age 63±16%; 5 male) with sustained VA and structural heart disease. Three patients had previous myocardial infarction; 1 cardiac sarcoidosis, 1 LMNA/C dilated cardiomyopathy and 1 post-myocarditis VA. LGE-CMR was available in all patients before the ULTC. At first, electro-anatomical mapping and VA induction were performed followed by ULTC using transseptal access. Each application consisted of freeze-thaw-freeze cycle with freeze duration at operator’s discretion based on manufacturer-recommended duration-depth curve. At the end, induction protocol was repeated to assess the acute success. Additionally, LGE-CMR was performed after ablation as an attempt to visualize the cryo-lesions. Results Median of 6 applications (IQR 4.75-7.5) of cryo-energy were applied per patient. Median procedure time was 180 min (IQR 97-180), and median fluoroscopy time of 20 min (IQR 15-26). Septal VA exits were detected in 3/6 patients; in 1 the exit was at aorto-mitral continuity; in 2 – basal inferior. After ablation, no VAs were inducible in 5/6 (83%) patients. The only patient with failure to ablate all VAs had fewer applications (n=4) and shorter freeze duration of 30 sec., as compared to the rest. Post-procedural CMR revealed new LGE with up to 75% transmurality in 5/6 patients; microvascular obstruction in 4/6 patients. Only LV edema, but no LGE was observed in the patient with shortest freeze time, who also had intra-hospital recurrence. No complications occurred. Conclusions Cryoablation of VA using a new ultra-low temperature technology is effective and safe to ablate VT even in patients with mid-septal substrates. New LGE in result of ULTCA can be observed in CMR and the lesions depth depends on the duration of application.

Pacemaker Channels and the Chronotropic Response in Health and Disease

Loss or dysregulation of the normally precise control of heart rate via the autonomic nervous system plays a critical role during the development and progression of cardiovascular disease—including ischemic heart disease, heart failure, and arrhythmias. While the clinical significance of regulating changes in heart rate, known as the chronotropic effect, is undeniable, the mechanisms controlling these changes remain not fully understood. Heart rate acceleration and deceleration are mediated by increasing or decreasing the spontaneous firing rate of pacemaker cells in the sinoatrial node. During the transition from rest to activity, sympathetic neurons stimulate these cells by activating β-adrenergic receptors and increasing intracellular cyclic adenosine monophosphate. The same signal transduction pathway is targeted by positive chronotropic drugs such as norepinephrine and dobutamine, which are used in the treatment of cardiogenic shock and severe heart failure. The cyclic adenosine monophosphate–sensitive hyperpolarization–activated current (I f ) in pacemaker cells is passed by hyperpolarization-activated cyclic nucleotide-gated cation channels and is critical for generating the autonomous heartbeat. In addition, this current has been suggested to play a central role in the chronotropic effect. Recent studies demonstrate that cyclic adenosine monophosphate–dependent regulation of HCN4 (hyperpolarization-activated cyclic nucleotide-gated cation channel isoform 4) acts to stabilize the heart rate, particularly during rapid rate transitions induced by the autonomic nervous system. The mechanism is based on creating a balance between firing and recently discovered nonfiring pacemaker cells in the sinoatrial node. In this way, hyperpolarization-activated cyclic nucleotide-gated cation channels may protect the heart from sinoatrial node dysfunction, secondary arrhythmia of the atria, and potentially fatal tachyarrhythmia of the ventricles. Here, we review the latest findings on sinoatrial node automaticity and discuss the physiological and pathophysiological role of HCN pacemaker channels in the chronotropic response and beyond.

Sociodemographic inequality in children aged 0–19 years with and without parents diagnosed with heart disease: a Danish nationwide register-based study

ObjectivesThis study aimed to estimate the prevalence of children aged 0–19 years who have a parent with a history of heart disease and investigate their sociodemographic characteristics. Study designA national register-based study. MethodsFrom the Danish Fertility Register and the Danish National Patient Register information on children of parents with ischemic heart disease, arrhythmia, heart failure and heart valve disease in the period 1981–2018 were obtained. Statistical analyses including descriptive statistics, logistic and linear regression were used to illuminate associations between parental heart disease and sociodemographic characteristics. ResultsThe study population consisted of 142,480 children aged 0–19 years with at least one parent diagnosed with heart disease, corresponding to every 9th child in Denmark in 2018. The number increased from 4.5% in 2002 to 11.1% in 2018. In the study population most had a father with heart disease (57.8%) and 4.6% had two parents with heart disease. Parents with heart disease had significantly higher odds of being out of work (OR 1.68, 95% CI 1.64; 1.72), in a single-parent household (OR 1.09, 95% CI 1.07; 1.11), divorced or widowed (OR: 1.10, 95% CI 1.08; 1.12), having a lower educational level (OR 1.35, 95% CI 1.33; 1.37), and a lower family income (−42,410 DKR, 95% CI -50,306; −34,514, P < 0.0001) compared to those without heart disease. ConclusionChildren affected by parental heart disease comprise a substantial part of the Danish population. These have significantly different sociodemographic characteristics than children in families without parental heart disease, which might affect social heritage and parental capacity.

Emerging Links Between COVID-19 and Cardiovascular &amp; Cerebrovascular Thromboembolic Events: A Systematic Review

Purpose: COVID-19, caused by the SARS-CoV-2 virus, initially identified as a respiratory illness, has increasingly been linked to a broader range of organ complications. This systematic review explores the impact of COVID-19 on cardiovascular and cerebrovascular health, focusing on thromboembolic events in post-COVID patients. Method: A comprehensive literature search was conducted in PubMed and Google Scholar databases up to July 2023, utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies meeting eligibility criteria were analyzed for outcomes and associations between COVID-19 and cardiovascular and cerebrovascular events. Result: The review includes 6 studies involving over 12 million patients, demonstrating a strong connection between COVID-19 and elevated risks of cardiovascular and cerebrovascular thromboembolic events. The risk of these events is evident in conditions such as ischemic heart disease, stroke, and cardiac arrhythmias. The burden of these events beyond the acute phase of the disease is concerning, warranting further exploration of long-term implications. Variability in event rates among different cohorts and healthcare settings underscores the need for understanding underlying factors influencing these differences. Potential mechanisms behind these events include endothelial dysfunction, systemic inflammation, and viral invasion. Implications for public health policies, clinical guidelines, and future research directions are discussed. Conclusion: This review serves as a valuable resource for healthcare providers, policymakers, and researchers to enhance patient care, outcomes, and preparedness for future waves of COVID-19 infections. However, there remain unexplored aspects of the COVID-19 and thromboembolic events relationship, urging further investigations into mechanistic insights and potential therapeutic interventions.

Grouped mixtures of air pollutants and seasonal temperature anomalies and cardiovascular hospitalizations among U.S. Residents

BackgroundAir pollution is a recognized risk factor for cardiovascular disease (CVD). Temperature is also linked to CVD, with a primary focus on acute effects. Despite the close relationship between air pollution and temperature, their health effects are often examined separately, potentially overlooking their synergistic effects. Moreover, fewer studies have performed mixture analysis for multiple co-exposures, essential for adjusting confounding effects among them and assessing both cumulative and individual effects. MethodsWe obtained hospitalization records for residents of 14 U.S. states, spanning 2000–2016, from the Health Cost and Utilization Project State Inpatient Databases. We used a grouped weighted quantile sum regression, a novel approach for mixture analysis, to simultaneously evaluate cumulative and individual associations of annual exposures to four grouped mixtures: air pollutants (elemental carbon, ammonium, nitrate, organic carbon, sulfate, nitrogen dioxide, ozone), differences between summer and winter temperature means and their long-term averages during the entire study period (i.e., summer and winter temperature mean anomalies), differences between summer and winter temperature standard deviations (SD) and their long-term averages during the entire study period (i.e., summer and winter temperature SD anomalies), and interaction terms between air pollutants and summer and winter temperature mean anomalies. The outcomes are hospitalization rates for four prevalent CVD subtypes: ischemic heart disease, cerebrovascular disease, heart failure, and arrhythmia. ResultsChronic exposure to air pollutant mixtures was associated with increased hospitalization rates for all CVD subtypes, with heart failure being the most susceptible subtype. Sulfate, nitrate, nitrogen dioxide, and organic carbon posed the highest risks. Mixtures of the interaction terms between air pollutants and temperature mean anomalies were associated with increased hospitalization rates for all CVD subtypes. ConclusionsOur findings identified critical pollutants for targeted emission controls and suggested that abnormal temperature changes chronically affected cardiovascular health by interacting with air pollution, not directly.