Double-device therapy in a patient with long QT syndrome.

A 26-year-old man with long QT syndrome (LQTS) underwent subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation. The patient exhibited sinus bradycardia relative to his age. The heart rate decreased, and the QT interval became longer with the administration of ß-blockers, the first-line therapy for LQTS. The patient experienced frequent S-ICD discharges. Subsequently, a single-chamber pacemaker was implanted, and the 12-lead electrocardiogram showed atrial pacing and ventricular sensing at 60 beats per minute with a shorter QTc interval. After converting to "double-device therapy," the patient did not experience any ventricular arrhythmia events.

Hybrid ablation for persistent atrial fibrillation: a narrative review.

Background and Objective: Treatment for atrial fibrillation (AF) has evolved significantly, with pulmonary vein isolation (PVI) becoming an established treatment. However, the outcomes following catheter ablation for persistent AF remain unsatisfactory. Hybrid catheter-surgical ablation has emerged as a therapeutic approach for persistent AF, combining the strengths of both interventions. The purpose of this narrative review is to comprehensively examine the current state of knowledge regarding hybrid ablation for AF. Methods: A thorough PubMed search using the terms "hybrid ablation", "atrial fibrillation", "catheter ablation", and "guideline on cardiology" within the timeframe of 1980 to 2024 resulted in 138,969 articles. Consensus on the selected articles was reached through a series of structured meetings and discussions. Key Content and Findings: PVI has demonstrated higher sinus rhythm maintenance rates, especially for paroxysmal AF. However, the efficacy is not as high for persistent AF. Additional ablation strategies, such as linear ablation, complex fractionated atrial electrogram ablation, low voltage zone ablation as well as posterior wall isolation, lack consistent evidence of effectiveness. Hybrid ablation, involving collaboration between cardiac surgeons and electrophysiologists, presents a promising alternative for hard-to-treat AF. Recent studies report favorable outcomes of hybrid ablation, with atrial arrhythmia-free rates ranging from 53.5% to 76%, surpassing those of catheter ablation alone, which might result from better lesion durability or intervention for non-PV foci and left atrial appendage excision or closure during hybrid ablation. The rate of complications associated with hybrid ablation is higher than catheter ablation alone. Conclusions: While favorable outcomes of hybrid ablation for persistent AF have been reported, it is not recommended for all AF patients due to its invasiveness compared to catheter ablation. Additionally, some patients with persistent AF maintain sinus rhythm with catheter ablation alone. More clinical data are needed to determine which patients are suitable candidates for hybrid ablation.

A case report of undetected cardiac arrest in a patient with an insertable cardiac monitor.

Insertable cardiac monitors (ICMs) are small electrocardiographs implanted subcutaneously to automatically record electrocardiograms when arrhythmia is detected in patients with syncope. If the ICM misses a significant arrhythmia, it may delay the diagnosis of arrhythmogenic syncope and put the patient at risk. Herein, we describe a case of undetected cardiac arrest in a patient with ICM. An 87-year-old man with syncope was admitted to the hospital. After 8 days of monitoring, the cause could not be determined, and an ICM was implanted. Nine hours after implantation, the patient experienced cardiopulmonary arrest. Despite a body surface electrocardiogram showing ventricular flatline and fibrillation, the ICM failed to record. The cause of failure to record was considered to be the fluctuation in the R-wave amplitude of the ICM and noise oversensing. In conclusion, albeit infrequently, ICMs might overlook life-threatening arrhythmias. Even in cases where the ICM fails to detect an arrhythmia matching the symptoms, it may not be feasible to entirely rule out the presence of arrhythmias. Learning objective: Insertable cardiac monitors (ICMs) are used to diagnose arrhythmogenic syncope. However, extremely infrequently, ICM may fail to record life-threatening arrhythmias. Failure to capture arrhythmias can happen due to an unfortunate combination of factors such as a low amplitude of the recorded R wave and noise. Even in cases where the ICM does not detect an arrhythmia that matches the symptoms, it may not be feasible to completely exclude the presence of arrhythmias.

Semi-urgent pulmonary vein isolation using cryoballoon for haemodynamically unstable atrial fibrillation storm in a patient with low cardiac output syndrome: a case report.

BACKGROUND: Atrial fibrillation and heart failure are common coexisting conditions requiring hospitalisation for heart failure and death. Pulmonary vein isolation is a well-established option for symptomatic atrial fibrillation and for atrial fibrillation concomitant with heart failure with reduced left ventricular ejection fraction. Recently, pulmonary vein isolation using cryoballoon showed non-inferiority to radiofrequency ablation with respect to the treatment of patients with drug-refractory paroxysmal atrial fibrillation. However, the effectiveness of acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon in patients with haemodynamically unstable atrial fibrillation storm accompanied with low cardiac output syndrome is unclear. Herein, we present a case in which semi-urgent pulmonary vein isolation using cryoballoon was effective for acute-phase rhythm control against drug-resistant and haemodynamically unstable repetitive atrial fibrillation tachycardia accompanied with low cardiac output syndrome. CASE PRESENTATION: A 57-year-old man was hospitalised for New York Heart Association functional class 4 heart failure with atrial fibrillation tachycardia and reduced left ventricular ejection fraction of 20% accompanied with low cardiac output syndrome-induced liver damage. The haemodynamics collapsed during atrial fibrillation tachycardia, which had become resistant to intravenous amiodarone and repeated electrical cardioversions. In addition to atrial fibrillation, atrial tachycardia and common-type atrial flutter appeared on day 3. Multiple organ failure progressed gradually due to haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome. On day 4, to focus on treatment of heart failure and multiple organ failure, semi-urgent rescue pulmonary vein isolation using cryoballoon to atrial fibrillation and cavotricuspid isthmus ablation to common-type atrial flutter were performed for acute-phase rhythm control. Soon after the ablation procedure, atrial fibrillation and common-type atrial flutter were lessened, and sinus rhythm was restored. A stable haemodynamics was successfully achieved with the improvement of hepatorenal function. The patient was discharged on day 77 without complications. CONCLUSIONS: This case demonstrates that acute-phase rhythm control by semi-urgent pulmonary vein isolation using cryoballoon could be a treatment option in patients with haemodynamically unstable atrial fibrillation tachycardia storm accompanied with low cardiac output syndrome, which is refractory to cardioversion and drug therapy.

Diversity of metabolic shift in response to oxygen deprivation in Corynebacterium glutamicum and its close relatives.

Oxygen-deprived Corynebacterium glutamicum R cells remain metabolically active, producing considerable amounts of organic acids even when not actively growing. We compared the proficiencies of C. glutamicum and close relatives grown under aerobic conditions to metabolize glucose when deprived of oxygen. Eight strains that readily consumed glucose without cell growth subsequently produced organic acids. Among these, the glucose consumption rates of the two C. glutamicum strains (>40 mM/h) and Corynebacterium efficiens (>12 mM/h) were an order of magnitude higher than those of the other five strains. The resultant organic acid yields of these three strains (>86%) consequently exceeded those of the other five (<60%). This difference is probably rooted in the comparatively inferior activities of glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and malate dehydrogenase observed in the five strains. Moreover, under oxygen deprivation, phosphoenolpyruvate carboxylase (PEPC) activity of C. efficiens was elevated tenfold, but its lack of fumarase activity meant that no succinic acid could be produced. The metabolic shift occasioned by addition of the PEPC substrate sodium bicarbonate resulted in a doubling of the glucose consumption rate of the two C. glutamicum strains but not that of the other six close relatives.

Increased bioavailability of tacrolimus after rectal administration in rats.

The oral bioavailability of tacrolimus is low and varies considerably in humans due to first-pass metabolism by cytochrome P450 (CYP) 3A4 and the active efflux mediated by P-glycoprotein. This study was undertaken to elucidate the usefulness of rectal administration of tacrolimus as an alternative route to improve its bioavailability. Tacrolimus powder was suspended in a suppository base (witepsol H-15) and the tacrolimus suppository was inserted into the anus of the rats. For comparison, tacrolimus was suspended in 0.5% sodium methylcellulose solution and administered orally to rats. The dose of tacrolimus was fixed to 2 mg/kg. Blood samples were collected periodically up to 24 h after dosing, and tacrolimus concentrations were assayed by microparticle enzyme immunoassay. The whole blood concentrations of tacrolimus after rectal administration were much greater than those after oral administration. The C(max) and AUC(0-24 h) values after rectal administration were 3.9- and 6.9-fold greater than those after oral administration, respectively. These results clearly suggest a possibility that rectal administration of tacrolimus is capable of improving its bioavailability and cutting the costs of tacrolimus treatment.

Biphenyl-inducible promoters in a polychlorinated biphenyl-degrading bacterium, Rhodococcus sp. RHA1.

Five transcriptional promoters of biphenyl-degradation genes in Rhodococcus sp. RHA1 were characterized. We newly identified the etbA4 promoter region, which was located adjacent upstream from a ferredoxin reductase gene, etbA4 and a dihydrodiol dehydrogenase gene, bphB2. The etbA4 promoter activity was determined in RHA1 using a promoter probe vector with a luxAB luciferase reporter gene, and was induced by a variety of aromatic compounds as well as the bphA1, ebdA1, etbA1, and etbD1 promoters. All these promoters were induced by aromatic compounds in a closely related heterologous host, R. erythropolis IAM1399 in the presence of RHA1 bphST genes, suggesting that these five promoters are under the control of bphST-coding two-component regulatory system. Sequence comparison of the bphA1 promoter with the ebdA1 and etbA1 promoters, whose transcription starts were determined by primer extension analysis, revealed a consensus sequence centering 42-bp upstream from the transcription start. This consensus was also conserved in the etbA4 and etbD1 promoters, and deletions of the bphA1 promoter affecting the consensus impaired inducible promoter activity. These results suggest that this consensus plays a role in transcription induction and/or the promotion of biphenyl degradation genes in RHA1.

2-Hydroxypenta-2,4-dienoate metabolic pathway genes in a strong polychlorinated biphenyl degrader, Rhodococcus sp. strain RHA1.

A gram-positive polychlorinated biphenyl (PCB) degrader, Rhodococcus sp. strain RHA1, metabolizes biphenyl through the 2-hydroxypenta-2,4-dienoate (HPD) and benzoate metabolic pathways. The HPD metabolic pathway genes, the HPD hydratase (bphE1), 4-hydroxy-2-oxovalerate aldolase (bphF1), and acetaldehyde dehydrogenase (acylating) (bphG) genes, were cloned from RHA1. The deduced amino acid sequences of bphGF1E1 have 30 to 58% identity with those of the HPD metabolic pathway genes of gram-negative bacteria. The order of these genes, bphG-bphF1-bphE1, differs from that of the HPD metabolic pathway genes, bphE-bphG-bphF, in gram-negative degraders of PCB, phenol, and toluene. Reverse transcription-PCR experiments indicated that the bphGF1E1 genes are inducibly cotranscribed in cells grown on biphenyl and ethylbenzene. Primer extension analysis revealed that the transcriptional initiation site exists within the bphR gene located adjacent to and upstream of bphG, which is deduced to code a transcriptional regulator. The respective enzyme activities of bphGF1E1 gene products were detected in Rhodococcus erythropolis IAM1399 carrying a bphGF1E1 plasmid. The insertional inactivation of the bphE1, bphF1, and bphG genes resulted in the loss of the corresponding enzyme activities and diminished growth on both biphenyl and ethylbenzene. Severe growth interference was observed during growth on biphenyl. The growth defects were partially restored by the introduction of plasmids containing the respective intact genes. These results indicated that the cloned bphGF1E1 genes are not only responsible for the primary metabolism of HPD during growth on both biphenyl and ethylbenzene but are also involved in preventing the accumulation of unexpected toxic metabolites, which interfere with the growth of RHA1.

Influence of nicardipine and nifedipine on plasma carvedilol disposition after oral administration in rats.

The effect of two kinds of 1,4-dihydropyridine calcium-channel blockers, nicardipine hydrochloride and nifedipine, on the disposition of carvedilol, was studied in rats. Blood samples were assayed for carvedilol levels using solid-phase extraction and high-performance liquid chromatography. The plasma carvedilol concentration was found to be significantly higher, and the area under the concentration-time curve up to 24 h (AUC0-->24) was 6.7 and 3.0 times higher after simultaneous oral administration of 20 mg kg(-1) carvedilol with 40 mg kg(-1) nicardipine hydrochloride, or with 40 mg kg(-1) nifedipine, respectively, than after administration of carvedilol alone. The pharmacokinetic interaction between carvedilol and dihydropyridine calcium-channel blockers is thought to be attributable to vasodilator-induced changes in hepatic first-pass metabolism, inhibition in the absorption barrier by P-glycoprotein and in the metabolism of carvedilol.

Diversity of 2,3-dihydroxybiphenyl dioxygenase genes in a strong PCB degrader, Rhodococcus sp. strain RHA1.

Two 2,3-dihydroxybiphenyl (23DHBP) dioxygenase genes, bphC1 and etbC involved in the degradation of polychlorinated biphenyl(s) (PCBs) have been isolated and characterized from a strong PCB degrader, Rhodococcus sp. RHA1. In this study, four new 23DHBP dioxygenase genes, designated as bphC2, bphC3, bphC4, and bphC5 were isolated from RHA1, and their nucleotide sequences were determined. Based on amino acid sequence similarities, all of the newly isolated bphC genes could be categorized into type I along with BphC1 and EtbC [Eltis, L.D. and Bolin, J.T., J. Bacteriol., 178, 5930-5937 (1996)]. Six bphC genes, including bphC1, etbC, and four new genes, were expressed in Escherichia coli to determine their substrate specificity. The activities of BphC2, BphC3, BphC4, and BphC5 were found to be specific to 23DHBP, while BphC1 and EtbC exhibited activities towards compounds other than 23DHBP, including catechol (CAT) and 3-methylcatechol (3MC). RNA slot blot hybridization analysis indicated that only bphC5 was transcribed among the newly isolated bphC in RHA1 cells grown on biphenyl and ethylbenzene. The nucleotide sequence of the flanking region of each bphC revealed a homolog of the 2-hydroxy-6-oxo-6-phenylhexa-2,4-dienoate (HOPD) hydrolase gene, bphD, just upstream of bphC5. The bphC5 and putative bphD genes may constitute an operon and play a role in the degradation of biphenyl and PCBs together with bphC1 and etbC. In contrast, the bphC2, bphC3, and bphC4 genes may not be involved in biphenyl and PCB degradation.