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.

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.

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.

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.

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.

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.

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.

The influence of cardiograph design and automated algorithms on the incidence and detection of electrode cable reversals in an academic electrocardiogram laboratory.

BACKGROUND: Medical errors have been increasingly identified as a major source of morbidity and mortality in both outpatient and acute care settings. Central to the evaluation of many medical problems, the 12-lead electrocardiogram (ECG) is susceptible to both technical and interpretative errors. Proper interpretation, however, is dependent on the quality and accuracy of the acquired ECG. METHODS: We evaluated the impact of both a newly designed electrocardiograph and a newly developed automated computer algorithm on the incidence and detection of electrode cable reversals (lead reversals). The study tested the association of the incidence of electrode cable reversals and the design of the connection terminal. The study was performed during a 7-month period preceding (53,875 ECGs) and after (53,344 ECGs) the implementation of the new system. Electrode cable reversals occurring in various sites of the medical center were tabulated and compared. We then sought to determine if computer detection algorithms could increase point-of-care detection of electrode cable reversals and, thereby, offset the influence of cardiograph design changes. Two commercially available automated detection algorithms were compared for their abilities to identify electrode cable reversals in our study population. RESULTS: During the 7-month postimplementation period, there was a significant increase in the incidence in electrode cable reversals (0.5% vs 0.1%, P < .001). The incidence of reversals for ECGs obtained in the emergency department was twice that of those obtained within the hospital (0.79% vs 0.38%, P < .01). Automated detection of electrode cable reversals from the 7-month study period increased from 38% to 71% (P < or = .0001), using a recently released automated algorithm supplied by the manufacturer. CONCLUSIONS: Electrode cable reversals are a prevalent source of medical errors that receives very little attention by the clinical community. The association of an increase in electrode cable reversals with an altered electrode cable connection terminal, coupled with an increased ability to detect electrode cable reversals using the manufacturer's recently developed algorithms, emphasizes the importance of ongoing research efforts to identify technical errors in electrocardiography.

Association between venous thromboembolism and perioperative allogeneic transfusion.

HYPOTHESIS: Perioperative allogeneic blood product transfusion would be associated with venous thromboembolic complications in surgical patients. DESIGN: Observational study using a state discharge database. SETTING: Nonfederal acute care hospitals in Maryland performing colorectal cancer resections between January 1, 1994, and December 31, 2000. PATIENTS: We obtained data on 14 014 adult patients having a primary diagnosis code for colorectal cancer and a primary procedure code for colorectal resection. MAIN OUTCOME MEASURES: The primary outcome variable was a discharge diagnosis of venous thromboembolism (VTE). RESULTS: Venous thromboembolism occurred in 1% of patients and was associated with an adjusted 3.8-fold increase in mortality (odds ratio, 3.8; 95% confidence interval, 2.1-6.8), a 61% increase in mean hospital length of stay, and a 72% increase in mean total hospital charges. Risk factors for VTE after adjustment included transfusion, female sex, age 80 years or older, moderate to severe liver disease vs no liver disease, admission through the emergency department, and low annual surgeon case volume. Transfusion was associated with an increase in the odds of developing VTE in women (odds ratio, 1.8; 95% confidence interval, 1.2-2.6) but not in men (odds ratio, 0.9; 95% confidence interval, 0.5-1.9). In the absence of transfusion, female compared with male sex was not associated with an increased risk of VTE (odds ratio, 1.2; 95% confidence interval, 0.8-1.7). CONCLUSIONS: In this large observational study of patients undergoing colorectal cancer resection, perioperative allogeneic blood transfusion was associated with an increased risk of VTE in women but not in men. Given the substantial morbidity and mortality associated with VTE and the implication that this finding has for postoperative management in women, this association must be confirmed in independent studies.

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.

Preoperative predictors of blood transfusion in colorectal cancer surgery.

Transfusion is associated with multiple risks and morbidities. Little is known, however, about preoperative predictors of transfusion in gastrointestinal surgery patients. To identify factors that influence transfusion practices, we analyzed hospital discharge data from colorectal cancer surgery patients in Maryland between 1994 and 2000 (n = 14,052). The primary outcome variable was whether or not patients received a blood product ("Any Transfusion"). Characteristics independently associated with an increased risk of receiving Any Transfusion included: advanced age (>80 yr: OR 2.3; 95% CI 1.9-2.9; 70-79 yr: OR 1.6; 95% CI 1.4-2.0 vs. <60 yr), moderate to severe liver disease (OR 2.5; 95% CI 1.5-4.2), mild liver disease (OR 2.1; 95% CI 1.5-2.9), diabetes with complications (OR 2.1; 95% CI 1.6-2.6), chronic renal disease (OR 2.1; 95% CI 1.4-3.0), female gender (OR 1.3; 95% CI 1.2-1.5), chronic pulmonary disease (COPD) (OR 1.3; 95% CI 1.1-1.4), and metastatic disease (OR 1.2; 95% CI 1.1-1.4). Patients at hospitals with an annual case volume in the highest quartile were at an increased risk for receiving Any Transfusion (OR 2.1; 95% CI 1.3-3.4) and those with surgeons in the highest volume quartile (>12 cases/yr) were at a decreased risk (OR 0.8; 95% CI 0.6-0.99). The association between greater surgeon case volume and low transfusion rates was seen in all but the very high volume hospitals (>74 cases/yr). Blood product transfusion was associated with a 2.5-fold (95% CI 2.1-3.1) increased mortality, 3.7 day (95% CI 2.1-3.1) increase in hospital length of stay, and a 7120 dollars (95% CI 6472 dollars-7769 dollars) increase in total charges compared to patients that did not receive Any Transfusion. This data can be used by providers in discussions with patients regarding the risks for transfusion and in identifying patients in whom strategies to reduce transfusions should be evaluated.

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.