Atrial fibrillation ablation in heart failure patients: Where do we stand in 2023? - State of the art review.

Atrial fibrillation (AF) and heart failure are common overlapping cardiovascular disorders. Despite important therapeutic advances over the past several decades, controversy persists about whether a rate control or rhythm control approach constitutes the best option in this population. There is also considerable debate about whether antiarrhythmic drug therapy or ablation is the best approach when rhythm control is pursued.  A brief historical examination of the literature addressing this issue will be performed. An analysis of several important clinical outcomes observed in the prospective, randomized studies, which have compared AF ablation to non-ablation treatment options, will be discussed. This review will conclude with recommendations to guide clinicians on the status of AF ablation as a treatment option when considering management options in heart failure patients with atrial fibrillation.

Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells.

Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.

Risk Profiles and Outcomes of Patients Receiving Cardiovascular Implantable Electronic Devices With and Without Antibacterial Envelopes.

Background The increasing use of cardiac implantable electronic devices (CIEDs) in a growing patient population has led to an even greater increase in CIED infection rates. Antibacterial CIED envelopes are often used as part of an infection risk-reduction strategy. However, best practices for when to use an envelope and which envelope to choose remain to be elucidated. Methods In this retrospective study, the records of 455 patients undergoing CIED implantation by a single surgeon were reviewed to identify trends in envelope use and outcomes after implantation through 12 months of follow-up. Of these patients, 165 were managed with a biologic antibacterial CIED envelope (CanGaroo®, Aziyo Biologics, Inc., Silver Spring, MD), 219 with a non-biologic envelope (Tyrx®, Medtronic Inc., Monmouth Junction, NJ), and 71 with no envelope. Results Most patients had two or more infection risk factors (77.9% with any envelope vs. 52.1% with no envelope; P < 0.001). Factors significantly associated with the use of an envelope included the history of heart failure, systemic anticoagulant use, the use of high-power or more complex devices, and reoperations. The overall rate of adverse events was 9.2% (n = 42). Rates of infection and hematoma were 1.8% and 2.6%, respectively. A decision tree is proposed that may aid clinical decision-making when considering CIED envelope usage. Conclusions There were no significant differences between groups in overall or individual adverse event rates. These data provide insight into real-world clinical decisions regarding the use of CIED envelopes and support the use of antibiotic-eluting CIED envelopes to limit infection risk in high-risk patients.

Electrical Storm in a Patient with Brugada Syndrome and Coronavirus Disease 2019.

Brugada syndrome (BrS) is an inherited arrhythmia syndrome characterized by right bundle branch block and dynamic ST-segment changes in precordial leads V1-V3. In patients with BrS, fever is a known trigger that may induce arrhythmia. For patients with BrS who contract coronavirus disease 2019 (COVID-19), the inflammatory response poses the risk of causing ventricular arrhythmias. The following case discusses the management of a patient with BrS presenting with electrical storm after contracting COVID-19. Treatment should be focused on aggressive anti-pyretic management along with concomitant pharmacological therapy.

Risk profiles and outcomes of patients receiving antibacterial cardiovascular implantable electronic device envelopes: A retrospective analysis.

BACKGROUND: Cardiovascular implantable electronic devices (CIEDs) are implanted in an increasing number of patients each year, which has led to an increase in the risk of CIED infection. Antibacterial CIED envelopes locally deliver antibiotics to the implant site over a short-term period and have been shown to reduce the risk of implant site infection. These envelopes are derived from either biologic or non-biologic materials. There is a paucity of data examining patient risk profiles and outcomes from using these envelope materials in the clinical setting and comparing these results to patients receiving no envelope with their CIED implantation. AIM: To evaluate risk profiles and outcomes of patients who underwent CIED procedures with an antibacterial envelope or no envelope. METHODS: After obtaining Internal Review Board approval, the records of consecutive patients who underwent a CIED implantation procedure by a single physician between March 2017 and December 2019 were retrospectively collected from our hospital. A total of 248 patients within this period were identified and reviewed through 12 mo of follow up. The CIED procedures used either no envelope (n = 57), a biologic envelope (CanGaroo®, Aziyo Biologics) that was pre-hydrated by the physician with vancomycin and gentamicin (n = 89), or a non-biologic envelope (Tyrx™, Medtronic) that was coated with a resorbable polymer containing the drug substances rifampin and minocycline by the manufacturer (n = 102). Patient selection for receiving either no envelope or an envelope (and which envelope to use) was determined by the treating physician. Statistical analyses were performed between the 3 groups (CanGaroo, Tyrx, and no envelope), and also between the No Envelope and Any Envelope groups by an independent, experienced biostatistician. RESULTS: On average, patients who received any envelope (biologic or non-biologic) were younger (70.7 ± 14.0 vs 74.9 ± 10.6, P = 0.017), had a greater number of infection risk factors (81.2% vs 49.1%, P < 0.001), received more high-powered devices (37.2% vs 5.8%, P = 0.004), and were undergoing more reoperative procedures (47.1% vs 0.0%, P < 0.001) than patients who received no envelope. Between the two envelopes, biologic envelopes tended to be used more often in higher risk patients (84.3% vs 78.4%) and reoperative procedures (62.9% vs 33.3%) than non-biologic envelopes. The rate of CIED implant site pocket infection was low (any envelope 0.5% vs no envelope 0.0%) and was statistically equivalent between the two envelope groups. Other reported adverse events (lead dislodgement, lead or pocket revision, device migration or erosion, twiddler's syndrome, and erythema/fever) were low and statistically equivalent between groups (biologic 2.2%, non-biologic 3.9%, no envelope 1.8%). CONCLUSION: CIED infection rates for biologic and non-biologic antibacterial envelopes are similar. Antibacterial envelopes may benefit patients who are higher risk for infection, however additional studies are warranted to confirm this.

Next-generation mapping with HD Grid and HD Wave.

High-definition (HD) mapping with the Advisor HD Grid and HD Wave Solution software offers unparalleled resolution in mapping complex arrhythmias. The unique shape of a HD Grid (16 electrodes in a 4 × 4 pattern) allows for the mapping of orthogonal electrograms (EGMs). In so doing, the HD Grid catheter virtually eliminates the issue of 'bipolar blindness', a phenomenon seen when a wavefront of propagation is traveling perpendicular to a bipole pair. By improving the accuracy of the 3D electroanatomical map, HD Grid offers the potential of shorter procedure times, safer ablations and higher success rates. The following article explores the role of HD Grid in mapping a variety of arrhythmias including supraventricular tachycardias, atrial fibrillation and ventricular tachycardia. In addition, the authors explore the role of HD Grid in more recently described substrate-based advanced mapping techniques.

Lay abstract Cardiac mapping is a minimally invasive procedure carried out in patients with abnormal heart rhythm arrhythmias. The procedure identifies and produces a map of the electrical activity of the heart. The unique shape of the Advisor HD Grid offers an advantage when mapping complex arrhythmias as it allows for a more detailed map of electrical activity in the heart. By improving the accuracy of the heart map, HD Grid could shorten procedure times, improve safety and increase success rates. The following article explores the role of HD Grid in mapping a variety of arrhythmias. In addition, the authors explore the role of HD Grid in more recently described substrate-based advanced mapping techniques.

Strategies for Managing Arrhythmias in Patients with Cardiac Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease that frequently involves the myocardium. Unfortunately, the sentinel manifestations of cardiac sarcoidosis are often potentially fatal bradyarrhythmia and tachyarrhythmia. Advanced imaging modalities such as cardiac magnetic resonance have allowed for increased diagnosis of cardiac involvement. The current review article explores diagnosis and treatment strategies for arrhythmias in patients with cardiac sarcoidosis.

Near infrared spectroscopy-guided exercise training for claudication in peripheral arterial disease.

RATIONALE: Supervised treadmill exercise for claudication in peripheral arterial disease is effective but poorly tolerated because of ischemic leg pain. Near infrared spectroscopy allows non-invasive detection of muscle ischemia during exercise, allowing for characterization of tissue perfusion and oxygen utilization during training. OBJECTIVE: We evaluated walking time, muscle blood flow, and muscle mitochondrial capacity in patients with peripheral artery disease after a traditional pain-based walking program and after a muscle oxygen-guided walking program. METHOD AND RESULTS: Patients with peripheral artery disease trained thrice weekly in 40-minute-long sessions for 12 weeks, randomized to oxygen-guided training ( n = 8, age 72 ± 9.7 years, 25% female) versus traditional pain-based training ( n = 10, age 71.6 ± 8.8 years, 20% female). Oxygen-guided training intensity was determined by maintaining a 15% reduction in skeletal muscle oxygenation by near infrared spectroscopy rather than relying on symptoms of pain to determine exercise effort. Pain free and maximal walking times were measured with a 12-minute Gardner treadmill test. Gastrocnemius mitochondrial capacity and blood flow were measured using near infrared spectroscopy. Baseline pain-free walking time was similar on a Gardner treadmill test (2.5 ± 0.9 vs. 3.6 ± 1.0 min, p = 0.5). After training, oxygen-guided cohorts improved similar to pain-guided cohorts (pain-free walking time 6.7 ± 0.9 vs. 6.9 ± 1.1 min, p < 0.01 for change from baseline and p = 0.97 between cohorts). Mitochondrial capacity improved in both groups but more so in the pain-guided cohort than in the oxygen-guided cohort (38.8 ± 8.3 vs. 14.0 ± 9.3, p = 0.018). Resting muscle blood flow did not improve significantly in either group with training. CONCLUSIONS: Oxygen-guided exercise training improves claudication comparable to pain-based training regimens. Adaptations in mitochondrial function rather than increases in limb perfusion may account for functional improvement. Increases in mitochondrial oxidative capacity may be proportional to the degree of tissue hypoxia during exercise.

A rapid evidence assessment of bleed-related healthcare resource utilization in publications reporting the use of direct oral anticoagulants for non-valvular atrial fibrillation.

Objective: Non-valvular atrial fibrillation (NVAF), a common cardiac arrhythmia, is associated with high morbidity and carries a substantial economic burden. Historically, vitamin K antagonists (VKAs; e.g. warfarin) have been used for therapy of NVAF, but recently several direct oral anticoagulants (DOACs) have been approved for prevention of stroke in patients with NVAF. This review summarizes the real-world evidence (RWE) for healthcare resource utilization (HRU) in patients receiving oral anticoagulants (VKAs and/or DOACs) for therapy of NVAF.Methods: A PRISMA-compliant literature search assessed Medline® and Embase® databases from 1 January 2011 to 4 May 2017, and the National Health Service Economic Evaluation Database from 1 January 2011 to 31 December 2015. Publications were included if they reported observational data from real-world use of one or more anticoagulant therapies. Outcomes of interest included hospitalizations, length of stay (LOS), mortality and costs.Results: Twenty-eight publications were included. Apixaban and dabigatran were associated with fewer bleed-related hospitalizations than warfarin. Bleed-related LOS were generally longer for warfarin than for DOACs. Bleed-related treatment costs were lower for patients receiving apixaban or receiving dabigatran than patients receiving rivaroxaban or receiving warfarin. Bleed-related mortality in patients receiving oral anticoagulation for treatment of NVAF were low across all DOACs and warfarin.Conclusions: The limited available evidence for HRU burden among patients receiving oral anticoagulation for NVAF suggests that DOACs (particularly apixaban and dabigatran) offer some degree of benefit in terms of HRU outcomes, compared with warfarin. Further work is required to understand HRU outcomes in patients receiving DOACs.

Reduced skeletal muscle oxidative capacity and impaired training adaptations in heart failure.

Systolic heart failure (HF) is associated with exercise intolerance that has been attributed, in part, to skeletal muscle dysfunction. The purpose of this study was to compare skeletal muscle oxidative capacity and training-induced changes in oxidative capacity in participants with and without HF. Participants with HF (n = 16, 65 ± 6.6 years) were compared with control participants without HF (n = 23, 61 ± 5.0 years). A subset of participants (HF: n = 7, controls: n = 5) performed 4 weeks of wrist-flexor exercise training. Skeletal muscle oxidative capacity was determined from the recovery kinetics of muscle oxygen consumption measured by near-infrared spectroscopy (NIRS) following a brief bout of wrist-flexor exercise. Oxidative capacity, prior to exercise training, was significantly lower in the HF participants in both the dominant (1.31 ± 0.30 min(-1) vs. 1.59 ± 0.25 min(-1), P = 0.002; HF and control groups, respectively) and nondominant arms (1.29 ± 0.24 min(-1) vs. 1.46 ± 0.23 min(-1), P = 0.04; HF and control groups, respectively). Following 4 weeks of endurance training, there was a significant difference in the training response between HF and controls, as the difference in oxidative training adaptations was 0.69 ± 0.12 min(-1) (P < 0.001, 95% CI 0.43, 0.96). The wrist-flexor training induced a ~50% improvement in oxidative capacity in participants without HF (mean difference from baseline = 0.66 ± 0.09 min(-1), P < 0.001, 95% CI 0.33, 0.98), whereas participants with HF showed no improvement in oxidative capacity (mean difference from baseline = -0.04 ± 0.08 min(-1), P = 0.66, 95% CI -0.24, 0.31), suggesting impairments in mitochondrial biogenesis. In conclusion, participants with HF had reduced oxidative capacity and impaired oxidative adaptations to endurance exercise compared to controls.

Hemiazygous coil placement for high-defibrillation thresholds in a patient with a right-sided implantable cardioverter defibrillator.

A 41-year-old man underwent implantation of a right-sided implantable cardioverter defibrillator after removal of an infected left-sided system. Defibrillation threshold (DFT) testing on the right-sided system failed to convert ventricular fibrillation at maximum device output (35 J) compared with a DFT of less than 15 J on the previous left-sided system. A single-coil lead was selectively placed into the hemiazygous vein, which courses leftward of the spine in a posterior-anterior projection, resulting in an improved shocking vector and reduction in DFTs to less than 25 J.

Atrial Fibrillation Complicating Acute Coronary Syndromes.

Atrial fibrillation frequently complicates myocardial infarction. Patients with atrial fibrillation complicating acute coronary syndrome have increased morbidity and mortality relative to patients that remain in normal sinus rhythm. No studies have identified a mortality benefit to rhythm control compared with rate control in the setting of acute coronary syndrome. Stroke prevention should be pursued with oral anticoagulation therapy, although the majority of patients with atrial fibrillation associated with acute coronary syndrome receive only antiplatelet therapy. There are several novel oral anticoagulant therapies now available, but these agents have not been well studied in combination with dual antiplatelet therapy. Therefore, warfarin as part of triple therapy is the most conservative approach until additional data becomes available.

The S1103Y cardiac sodium channel variant is associated with implantable cardioverter-defibrillator events in blacks with heart failure and reduced ejection fraction.

BACKGROUND: Risk-stratifying heart failure patients for primary prevention implantable cardioverter-defibrillators (ICDs) remains a challenge, especially for blacks, who have an increased incidence of sudden cardiac death but have been underrepresented in clinical trials. We hypothesized that the S1103Y cardiac sodium channel SCN5A variant influences the propensity for ventricular arrhythmias in black patients with heart failure and reduced ejection fraction. METHODS AND RESULTS: Blacks (n=112) with ejection fractions <35% receiving primary prevention ICDs were identified from the Duke Electrophysiology Genetic and Genomic Studies (EPGEN) biorepository and followed for appropriate ICD therapy (either anti tachycardia pacing or shock) for documented sustained ventricular tachycardia or fibrillation. The S1103Y variant was overrepresented in patients receiving appropriate ICD therapy compared with subjects who did not (35% versus 13%, P=0.03). Controlling for baseline characteristics, the adjusted hazard ratio using a Cox proportional hazard model for ICD therapy in Y1103 allele carriers was 4.33 (95% confidence interval, 1.60 to 11.73, P=<0.01). There was no difference in mortality between carriers and noncarriers. CONCLUSIONS: This is the first report that the S1103Y variant is associated with a higher incidence of ventricular arrhythmias in blacks with heart failure and reduced ejection fraction.

Atrial fibrillation management strategies and early mortality after myocardial infarction: results from the Valsartan in Acute Myocardial Infarction (VALIANT) Trial.

OBJECTIVE: The management of patients with atrial fibrillation (AF) following a myocardial infarction (MI) remains uncertain. This study compared a rate control strategy to an anti-arrhythmic-based rhythm control strategy for the treatment of AF following myocardial infarction. DESIGN, SETTING AND PATIENTS: We studied 1131 patients with AF after MI who were enrolled in the Valsartan in Acute Myocardial Infarction Trial (VALIANT). We classified patients into those treated with a rhythm control strategy (n=371) and those treated with a rate control strategy (n=760). MAIN OUTCOMES MEASURES: Using Cox models, we compared the two groups with respect to both death and stroke during two different time periods after randomisation for which data collection had been pre-specified: 0-45 days and 45-1096 days. RESULTS: After adjustment, a rhythm control strategy was found to be associated with increased early mortality (0-45 days: HR: 1.9, 95% CI 1.2 to 3.0, p=0.004) but not late mortality (45-1096 days: HR 1.1, 95% CI 0.9 to 1.4, p=0.45). No difference was observed in the incidence of stroke (0-45 days: HR 1.2, 95% CI 0.4 to 3.7, p=0.73; 45-1096 days: HR 0.6, 95% CI 0.3 to 1.3, p=0.21). CONCLUSIONS: In patients with AF after an MI, an anti-arrhythmic drug-based rhythm control strategy is associated with excess 45-day mortality compared with a rate control strategy, but is not associated with increased mortality outside of the immediate peri-infarct period. These results potentially identify a patient population in whom the use of anti-arrhythmic drug therapy may portend an increased risk of death.

Cholinergic augmentation of insulin release requires ankyrin-B.

Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R and is enriched in pancreatic beta cells. We found that ankyrin-B-deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca2+ release, and reduced the abundance of IP3R. Ankyrin-B-haploinsufficient mice exhibited hyperglycemia after oral ingestion but not after intraperitoneal injection of glucose, consistent with impaired parasympathetic potentiation of glucose-stimulated insulin secretion. The R1788W mutation of ankyrin-B impaired its function in pancreatic islets and is associated with type 2 diabetes in Caucasians and Hispanics. Thus, defective glycemic regulation through loss of ankyrin-B-dependent stabilization of IP3R is a potential risk factor for type 2 diabetes.

Ankyrin-based patterning of membrane microdomains: new insights into a novel class of cardiovascular diseases.

The organization of membrane-spanning proteins within discrete microdomains is critical for their physiologic function. This is especially important in the heart, where ion transporter and force-transducing microdomains are responsible for excitation-contraction coupling, anisotropic depolarization, and mechanotransduction. The following review will discuss recent advances in our understanding of the patterning of ion channel and force-transmitting membrane microdomains in cardiomyocytes, focusing on the T-tubule and intercalated disc.