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Pharmaceuticals (Basel, Switzerland) May 2024Amiodarone is an anti-arrhythmic drug that has extensive tissue distribution and substantial storage in the fat tissue. Different studies have described some...
BACKGROUND
Amiodarone is an anti-arrhythmic drug that has extensive tissue distribution and substantial storage in the fat tissue. Different studies have described some implications of body fat composition in its pharmacokinetics and pharmacodynamics. However, no clinical studies have described its implications for clinical efficacy.
METHODS
We studied 878 patients with persistent atrial fibrillation (AF) treated with a regimen of amiodarone and referred to electrical cardioversion (ECV), included prospectively in two Spanish registries. We analyzed the influence of body mass index (BMI), as well as overweight and obesity, in the efficacy of amiodarone for achieving pharmacologic cardioversion to sinus rhythm (SR) before ECV.
RESULTS
A total of 185 patients (21.1%) reverted to SR before ECV. Patients who reverted to SR had a lower BMI than those who did not revert (27.45 ± 4.36 kg/m vs. 29.11 ± 4.09 kg/m; < 0.001). We observed a progressively lower probability of reverting to SR in overweight and obese patients (normal weight 28.3%, overweight 21.3%, obesity 13.1%; < 0.001). In the logistic regression, BMI (kg/m) adjusted for other related variables remained as the main factor inversely related to reversion to SR (OR = 0.904 × kg/m); CI 75% 0.864-0.946).
CONCLUSIONS
We observed a negative relationship between an increased BMI and the efficacy of amiodarone for reversion to SR, suggesting a negative clinical impact of excess body fat in its efficacy.
PubMed: 38931360
DOI: 10.3390/ph17060693 -
Annals of Noninvasive Electrocardiology... Jul 2024In this case report, we describe a patient who presented with chronic symptoms and signs of uremia and persistent accelerated idioventricular rhythm (AIVR) on...
In this case report, we describe a patient who presented with chronic symptoms and signs of uremia and persistent accelerated idioventricular rhythm (AIVR) on electrocardiogram. Findings from blood tests, echocardiography, renal ultrasound, and renal scan were suggestive of heart failure with reduced ejection fraction and chronic kidney disease, and attendance of daily hemodialysis sessions led to the restoration of sinus rhythm. Typically, AIVR has a favorable prognosis and, if necessary, medical intervention focuses on addressing the underlying responsible causes. Accumulation of uremic toxins has the potential to trigger the formation of AIVR and clearance of small solutes through conventional hemodialysis may contribute to sinus rhythm restoration.
Topics: Humans; Electrocardiography; Accelerated Idioventricular Rhythm; Male; Cardio-Renal Syndrome; Renal Dialysis; Middle Aged; Echocardiography
PubMed: 38923781
DOI: 10.1111/anec.13131 -
Cureus May 2024Cognitive communication abilities, such as working memory (WM), are vital for accomplishing daily activities and are also important for higher-order processes such as...
BACKGROUND
Cognitive communication abilities, such as working memory (WM), are vital for accomplishing daily activities and are also important for higher-order processes such as planning and problem-solving. The current study investigates the simultaneous effect of kapalabhati (KBH) on WM and phasic heart rate variability (HRV).
METHODS
Twenty participants who fulfilled the inclusion and exclusion criteria, with an average age of 23.65±3.07 years (mean±SD), were recruited for the study. Prior to data collection, the participants underwent a seven-day orientation to maintain uniformity in KBH practice. EKGs were assessed using a 16-channel polygraph system arranged in a standard limb lead II configuration. WM was assessed using E-Prime version 2.0 (Psychology Software Tools, Sharpsburg, PA, USA).
RESULTS
There was a significant increase in accuracy after the immediate KBH practice in all three conditions of the WM task (i.e., n-back task: 0-back, 1-back, and 2-back). However, there was also an increase in reaction time. Repeated measures ANOVA of HRV measures showed statistically significant changes in mean rhythm-to-rhythm (RR) intervals, heart rate (HR), number of adjacent N-N intervals over 50 milliseconds (NN50), percentage of successive normal sinus RR intervals greater than 50 milliseconds (pNN50 RR), low frequency (LF), and high frequency (HF), with HR, NN50, pNN50, LF, and HF all significant at p<0.001 and the LF/HF ratio significant at the p<0.01 level.
CONCLUSION
The results of the current study suggest that KBH practice can modulate vagal tone or parasympathetic activity and improve WM performance. Furthermore, the parasympathetic shift found in the present study may promote better cardioprotective health and longevity.
PubMed: 38915978
DOI: 10.7759/cureus.61027 -
Circulation Jun 2024Alterations in the buffering of intracellular Ca, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that...
BACKGROUND
Alterations in the buffering of intracellular Ca, for which myofilament proteins play a key role, have been shown to promote cardiac arrhythmia. It is interesting that although studies report atrial myofibrillar degradation in patients with persistent atrial fibrillation (persAF), the intracellular Ca buffering profile in persAF remains obscure. Therefore, we aim to investigate the intracellular buffering of calcium and its potential arrhythmogenic role in persAF.
METHODS
Simultaneous transmembrane fluxes (patch-clamp) and intracellular Ca signaling (fluo-3-acetoxymethyl ester) were recorded in myocytes from right atrial biopsies of sinus rhythm (control) and patients with persAF, alongside human atrial subtype induced pluripotent stem cell-derived cardiac myocytes (iPSC-CMs). Protein levels were quantified by immunoblotting of human atrial tissue and induced pluripotent stem cell-derived cardiac myocytes. Mouse whole heart and atrial electrophysiology was measured on a Langendorff system.
RESULTS
Cytosolic Ca buffering was decreased in atrial myocytes of patients with persAF because of a depleted amount of Ca buffers. In agreement, protein levels of selected Ca binding myofilament proteins, including cTnC (cardiac troponin C), a major cytosolic Ca buffer, were significantly lower in patients with persAF. Small interfering RNA (siRNA)-mediated knockdown of cTnC in induced pluripotent stem cell-derived cardiac myocytes (si-cTnC) phenocopied the reduced cytosolic Ca buffering observed in persAF. Si-cTnC induced pluripotent stem cell-derived cardiac myocytes exhibited a higher predisposition to spontaneous Ca release events and developed action potential alternans at low stimulation frequencies. Last, indirect reduction of cytosolic Ca buffering using blebbistatin in an ex vivo mouse whole heart model increased vulnerability to tachypacing-induced atrial arrhythmia, validating the direct mechanistic link between impaired cytosolic Ca buffering and atrial arrhythmogenesis.
CONCLUSIONS
Our findings suggest that loss of myofilament proteins, particularly reduced cTnC protein levels, causes diminished cytosolic Ca buffering in persAF, thereby potentiating the occurrence of spontaneous Ca release events and AF susceptibility. Strategies targeting intracellular buffering may represent a promising therapeutic lead in AF management.
PubMed: 38910563
DOI: 10.1161/CIRCULATIONAHA.123.066577 -
BMC Cardiovascular Disorders Jun 2024Electrophysiological characteristics and radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) originating from the superior septal left...
BACKGROUND AND AIMS
Electrophysiological characteristics and radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) originating from the superior septal left ventricle (SSLV) have not yet been fully characterized.
METHODS AND RESULTS
This study included 247 patients who underwent RFCA for PVCs arising from the ventricular outflow tract between February 2020 and August 2022. The successful ablation site was on the SSLV in 37 of the 247 patients. In 12 (32.4%) of those 37 patients, a low amplitude and high frequency spiky potential (SP) was recognized. Five patients showed a narrow QRS duration (86.8 ± 4.6 ms), with a discrete SP observed in PVCs and sinus rhythm, which showed an isoelectric line with the ventricular electrogram at the earliest activation site. Seven patients showed a wide QRS duration (131.6 ± 4.5 ms), with SP observed in PVCs without an isoelectric line with the ventricular electrogram. RFCA was successful at the site of the earliest SP in all 12 patients. The time from SP onset at the successful ablation site to the QRS onset (local activation time) was 30 ± 12 ms, which differed significantly from that for the remaining 25 patients withoutSP(22.1 ± 7.1 ms, P < 0.05).
CONCLUSIONS
SPs were recorded in 12 (32.4%) of the 37 patients with PVCs originating from the SSLV. The morphology of the PVCs may show a narrow or wide QRS duration and the target site for successful ablation should be identified by the earliest SP.
Topics: Humans; Catheter Ablation; Ventricular Premature Complexes; Male; Female; Middle Aged; Treatment Outcome; Action Potentials; Electrophysiologic Techniques, Cardiac; Adult; Heart Rate; Time Factors; Retrospective Studies; Aged; Electrocardiography
PubMed: 38910261
DOI: 10.1186/s12872-024-03979-9 -
NPJ Microgravity Jun 2024Deep-space missions require preventative care methods based on predictive models for identifying in-space pathologies. Deploying such models requires flexible edge...
Deep-space missions require preventative care methods based on predictive models for identifying in-space pathologies. Deploying such models requires flexible edge computing, which Open Neural Network Exchange (ONNX) formats enable by optimizing inference directly on wearable edge devices. This work demonstrates an innovative approach to point-of-care machine learning model pipelines by combining this capacity with an advanced self-optimizing training scheme to classify periods of Normal Sinus Rhythm (NSR), Atrial Fibrillation (AFIB), and Atrial Flutter (AFL). 742 h of electrocardiogram (ECG) recordings were pre-processed into 30-second normalized samples where variable mode decomposition purged muscle artifacts and instrumentation noise. Seventeen heart rate variability and morphological ECG features were extracted by convoluting peak detection with Gaussian distributions and delineating QRS complexes using discrete wavelet transforms. The decision tree classifier's features, parameters, and hyperparameters were self-optimized through stratified triple nested cross-validation ranked on F1-scoring against cardiologist labeling. The selected model achieved a macro F1-score of 0.899 with 0.993 for NSR, 0.938 for AFIB, and 0.767 for AFL. The most important features included median P-wave amplitudes, PRR20, and mean heart rates. The ONNX-translated pipeline took 9.2 s/sample. This combination of our self-optimizing scheme and deployment use case of ONNX demonstrated overall accurate operational tachycardia detection.
PubMed: 38909067
DOI: 10.1038/s41526-024-00409-0 -
Cardiovascular Pathology : the Official... Jun 2024The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs... (Review)
Review
The potential of the pericardial space as a therapeutic delivery tool for cardiac fibrosis and heart failure (HF) treatment has yet to be elucidated. Recently, miRNAs and exosomes have been discovered to be present in human pericardial fluid (PF). Novel studies have shown characteristic human PF miRNA compositions associated with cardiac diseases and higher miRNA expressions in PF compared to peripheral blood. Five key studies found differentially expressed miRNAs in HF, angina pectoris, aortic stenosis, ventricular tachycardia, and congenital heart diseases with either atrial fibrillation or sinus rhythm. As miRNA-based therapeutics for cardiac fibrosis and HF showed promising results in several in vivo studies for multiple miRNAs, we hypothesize a potential role of miRNA-based therapeutics delivered through the pericardial cavity. This is underlined by the favorable results of the first phase 1b clinical trial in this emerging field. Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods.
PubMed: 38906439
DOI: 10.1016/j.carpath.2024.107671 -
Cureus May 2024A 37-year-old woman was admitted to our hospital due to a loss of consciousness. She had been taking 2 mg of tizanidine for two months to manage shoulder muscle pain at...
A 37-year-old woman was admitted to our hospital due to a loss of consciousness. She had been taking 2 mg of tizanidine for two months to manage shoulder muscle pain at night. On admission, an electrocardiogram showed sinus bradycardia with a heart rate of 30 bpm and QT prolongation (QTc 495 msec). She had a temporary pacemaker inserted in the catheterization room, after which an improvement in her level of consciousness was observed. There were no apparent endocrine disorders or structural heart diseases. The administration was discontinued after admission, and 12 hours after admission, her heart rate normalized to a sinus rhythm of 70-100 bpm, and QTc improved to 431 msec. Therefore, she was diagnosed with tizanidine-induced bradycardia. Although reports of tizanidine-induced bradycardia are rare, tizanidine's central α2 agonistic effects can cause bradycardia, necessitating caution.
PubMed: 38894773
DOI: 10.7759/cureus.60581 -
Journal of Clinical Medicine Jun 2024: The effectiveness of a rhythm control strategy in patients with atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF < 50%) in real-world...
: The effectiveness of a rhythm control strategy in patients with atrial fibrillation (AF) and reduced left ventricular ejection fraction (LVEF < 50%) in real-world practice remains uncertain. Our objective was to evaluate the real-world outcomes of a rhythm control strategy in patients with AF and reduced LVEF, focusing on changes in LV systolic function and brain natriuretic peptide (BNP) levels. : The study retrospectively reviewed the medical records of 80 patients with concurrent AF and reduced LVEF who underwent rhythm control therapy between March 2015 and December 2021. : The patients had an average age of 63.6 years and an initial LVEF of 34.3%. Sinus rhythm was restored using anti-arrhythmic drugs (38, 47.5%) or electrical cardioversion (42, 52.5%). Over a follow-up period of 53.0 months, AF recurred in 65% of patients, with 57.7% undergoing catheter ablation. Significant improvements were noted in LVEF (from 34.3% to 55.1%, < 0.001) and BNP levels (from 752 pg/mL to 72 pg/mL, < 0.001) at the last follow-up. Nearly all patients (97.5%) continued with the rhythm control strategy during the follow-up period. : In real-world settings, a rhythm control strategy proves to be feasible and effective for improving LVEF and reducing BNP levels in AF patients with reduced LVEF.
PubMed: 38892996
DOI: 10.3390/jcm13113285 -
Journal of Clinical Medicine May 2024: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and...
: TOMM40 single nucleotide polymorphism (SNP) rs2075650 consists of allelic variation c.275-31A > G and it has been linked to Alzheimer disease, apolipoprotein and cholesterol levels and other risk factors. However, data on its role in cardiovascular disorders are lacking. The first aim of the study is to evaluate mortality according to TOMM40 genotype in a cohort of selected patients affected by advanced atherosclerosis. Second aim was to investigate the relationship between Xg and AA alleles and the presence of conduction disorders and implantation of defibrillator (ICD) or pacemaker (PM) in our cohort. : We enrolled 276 patients (mean age 70.16 ± 7.96 years) affected by hemodynamic significant carotid stenosis and/or ischemia of the lower limbs of II or III stadium Fontaine. We divided the population into two groups according to the genotype (Xg and AA carriers). We evaluated several electrocardiographic and echocardiographic parameters, including heart rate, rhythm, presence of right and left bundle branch block (LBBB and RBBB), PR interval, QRS duration and morphology, QTc interval, and left ventricular ejection fraction (LVEF). We clinically followed these patients for 82.53 ± 30.02 months and we evaluated the incidence of cardiovascular events, number of deaths and PM/ICD implantations. We did not find a difference in total mortality between Xg and AA carriers (16.3 % vs. 19.4%; = 0.62). However, we found a higher mortality for fatal cardiovascular events in Xg carriers (8.2% vs. 4.4%; HR = 4.53, 95% CI 1.179-17.367; = 0.04) with respect to AA carriers. We noted a higher percentage of LBBB in Xg carriers (10.2% vs. 3.1%, = 0.027), which was statistically significant. Presence of right bundle branch block (RBBB) was also higher in Xg (10.2% vs. 4.4%, = 0.10), but without reaching statistically significant difference compared to AA patients. We did not observe significant differences in heart rate, presence of sinus rhythm, number of device implantations, PR and QTc intervals, QRS duration and LVEF between the two groups. At the time of enrolment, we observed a tendency for device implant in Xg carriers at a younger age compared to AA carriers (58.50 ± 0.71 y vs. 72.14 ± 11.11 y, = 0.10). During the follow-up, we noted no statistical difference for new device implantations in Xg respect to AA carriers (8.2% vs. 3.5%; HR = 2.384, 95% CI 0.718-7.922; = 0.156). The tendency to implant Xg at a younger age compared to AA patients was confirmed during follow-up, but without reaching a significant difference(69.50 ± 2.89 y vs. 75.63 ± 8.35 y, = 0.074). Finally, we pointed out that Xg carriers underwent device implantation 7.27 ± 4.43 years before AA (65.83 ± 6.11 years vs. 73.10 ± 10.39 years) and that difference reached a statistically significant difference ( = 0.049) when we considered all patients, from enrollment to follow-up. : In our study we observed that TOMM40 Xg patients affected by advanced atherosclerosis have a higher incidence of developing fatal cardiovascular events, higher incidence of LBBB and an earlier age of PM or ICD implantations, as compared to AA carriers. Further studies will be needed to evaluate the genomic contribution of TOMM40 SNPs to cardiovascular deaths and cardiac conduction diseases.
PubMed: 38892888
DOI: 10.3390/jcm13113177