Clinical Outcomes of Early Rhythm or Rate Control for New Onset Atrial Fibrillation Following Transcatheter Aortic Valve Replacement.

BACKGROUND: New onset atrial fibrillation (NOAF) is a common occurrence after transcatheter aortic valve replacement (TAVR) and portends a poorer prognosis. The optimal strategy for managing NOAF in this population is uncertain. METHODS: This retrospective cohort study utilized deidentified patient data from the TriNetX Research Network. Patients with TAVR and NOAF were stratified into a rhythm control cohort if they were treated with antiarrhythmics, received AF ablation, or underwent cardioversion within 1 year of AF diagnosis. A rate control cohort was similarly defined by the absence of rhythm control strategies and treatment with a beta blocker, calcium channel blocker, or digoxin. After 1:1 propensity score matching, the Kaplan-Meier survival analysis and Cox proportional hazard ratios (HRs) were used to compare outcomes at 7 years of follow-up. RESULTS: We identified 569 patients in each cohort following propensity matching. At 7 years, the primary composite outcome of all-cause death, myocardial infarction, cerebrovascular accident, and heart failure hospitalization was not significantly different between the rhythm and rate control cohorts (HR 0.99, 95% CI 0.83-1.18). The individual components of the primary outcome in addition to all-cause hospitalization were also similar between the groups. CONCLUSIONS: Similar outcomes were seen among patients receiving an early rhythm or rate control strategy to manage NOAF after TAVR. The attenuated benefits of an early rhythm control strategy observed in this setting may be due to the overall high burden of comorbidities and advanced age of these patients.

Cardiac conduction diseases: understanding the molecular mechanisms to uncover targets for future treatments.

INTRODUCTION: The cardiac conduction system (CCS) is crucial for maintaining adequate cardiac frequency at rest and modulation during exercise. Furthermore, the atrioventricular node and His-Purkinje system are essential for maintaining atrioventricular and interventricular synchrony and consequently maintaining an adequate cardiac output. AREAS COVERED: In this review article, we examine the anatomy, physiology, and pathophysiology of the CCS. We then discuss in detail the most common genetic mutations and the molecular mechanisms of cardiac conduction disease (CCD) and provide our perspectives on future research and therapeutic opportunities in this field. EXPERT OPINION: Significant advancement has been made in understanding the molecular mechanisms of CCD, including the recognition of the heterogeneous signaling at the subcellular levels of sinoatrial node, the involvement of inflammatory and autoimmune mechanisms, and the potential impact of epigenetic regulations on CCD. However, the current treatment of CCD manifested as bradycardia still relies primarily on cardiovascular implantable electronic devices (CIEDs). On the other hand, an If specific inhibitor was developed to treat inappropriate sinus tachycardia and sinus tachycardia in heart failure patients with reduced ejection fraction. More work is needed to translate current knowledge into pharmacologic or genetic interventions for the management of CCDs.

Innovations in atrial fibrillation ablation.

BACKGROUND: Catheter-based ablation to perform pulmonary vein isolation (PVI) has established itself as a mainstay in the rhythm control strategy of atrial fibrillation. This review article aims to provide an overview of recent advances in atrial fibrillation ablation technology. METHODS: We reviewed the available literature and clinical trials of innovations in atrial fibrillation ablation technologies including ablation catheter designs, alternative energy sources, esophageal protection methods, electroanatomical mapping, and novel ablation targets. RESULTS: Innovative radiofrequency (RF) catheter designs maximize energy delivery while avoiding overheating associated with conventional catheters. Single-shot balloon catheters in the form of cryoballoons, radiofrequency, and laser balloons have proven effective at producing pulmonary vein isolation and improving procedural efficiency and reproducibility. Pulsed field ablation (PFA) is a highly anticipated novel nonthermal energy source under development, which demonstrates selective ablation of the myocardium, producing durable lesions while also minimizing collateral damage. Innovative devices for esophageal protection including esophageal deviation and cooling devices have been developed to reduce esophageal complications. Improved electroanatomical mapping systems are being developed to help identify additional non-pulmonary triggers, which may benefit from ablation, especially with persistent atrial fibrillation. Lastly, the vein of Marshall alcohol ablation has been recently studied as an adjunct therapy for improving outcomes with catheter ablation for persistent atrial fibrillation. CONCLUSIONS: Numerous advances have been made in the field of atrial fibrillation ablation in the past decade. While further long-term data is still needed for these novel technologies, they show potential to improve procedural efficacy and safety.

Innovations in ventricular tachycardia ablation.

Catheter ablation of ventricular arrhythmias (VAs) has evolved significantly over the past decade and is currently a well-established therapeutic option. Technological advances and improved understanding of VA mechanisms have led to tremendous innovations in VA ablation. The purpose of this review article is to provide an overview of current innovations in VA ablation. Mapping techniques, such as ultra-high density mapping, isochronal late activation mapping, and ripple mapping, have provided improved arrhythmogenic substrate delineation and potential procedural success while limiting duration of ablation procedure and potential hemodynamic compromise. Besides, more advanced mapping and ablation techniques such as epicardial and intramyocardial ablation approaches have allowed operators to more precisely target arrhythmogenic substrate. Moreover, advances in alternate energy sources, such as electroporation, as well as stereotactic radiation therapy have been proposed to be effective and safe. New catheters, such as the lattice and the saline-enhanced radiofrequency catheters, have been designed to provide deeper and more durable tissue ablation lesions compared to conventional catheters. Contact force optimization and baseline impedance modulation are important tools to optimize VT radiofrequency ablation and improve procedural success. Furthermore, advances in cardiac imaging, specifically cardiac MRI, have great potential in identifying arrhythmogenic substrate and evaluating ablation success. Overall, VA ablation has undergone significant advances over the past years. Innovations in VA mapping techniques, alternate energy source, new catheters, and utilization of cardiac imaging have great potential to improve overall procedural safety, hemodynamic stability, and procedural success.

Late Gadolinium Enhancement Magnetic Resonance Imaging Evaluation of Post-Atrial Fibrillation Ablation Esophageal Thermal Injury Across the Spectrum of Severity.

Background Esophageal thermal injury (ETI) is a byproduct of atrial fibrillation (AF) ablation using thermal sources. The most severe form of ETI is represented by atrioesophageal fistula, which has a high mortality rate. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) allows identification of ETI. Hence, we sought to evaluate the utility of LGE-MRI as a method to identify ETI across the entire spectrum of severity. Methods and Results All AF radiofrequency ablations performed at the University of Utah between January 2009 and December 2017 were reviewed. Patients with LGE-MRI within 24 hours following AF ablation as well as patients who had esophagogastroduodenoscopy in addition to LGE-MRI were identified. An additional patient with atrioesophageal fistula who had AF ablation at a different institution and had MRI and esophagogastroduodenoscopy at the University of Utah was identified. A total of 1269 AF radiofrequency ablations were identified. ETI severity was classified on the basis of esophageal LGE pattern (none, 60.9%; mild, 27.5%; moderate, 9.9%; severe, 1.7%). ETI resolved in most patients who underwent repeat LGE-MRI at 3 months. All patients with esophagogastroduodenoscopy-confirmed ETI had moderate-to-severe LGE 24 hours after ablation MRI. Moderate-to-severe LGE had 100% sensitivity and 58.1% specificity in detecting ETI, and a negative predictive value of 100%. Atrioesophageal fistula was visualized by both computed tomography and LGE-MRI in one patient. Conclusions LGE-MRI is useful in detecting and characterizing ETI across the entire severity spectrum. LGE-MRI exhibits an extremely high sensitivity and negative predictive value in screening for ETI after AF ablation.

Predicting mortality in cardiogenic shock secondary to ACS requiring short-term mechanical circulatory support: The ACS-MCS score.

OBJECTIVE: To identify predictors of 30-day all-cause mortality for patients with cardiogenic shock secondary to acute coronary syndrome (ACS-CS) who require short-term mechanical circulatory support (ST-MCS). BACKGROUND: ACS-CS mortality is high. ST-MCS is an attractive treatment option for hemodynamic support and stabilization of deteriorating patients. Mortality prediction modeling for ACS-CS patients requiring ST-MCS has not been well-defined. METHODS: The Utah Cardiac Recovery (UCAR) Shock database was used to identify patients admitted with ACS-CS requiring ST-MCS devices between May 2008 and August 2018. Pre-ST-MCS clinical, laboratory, echocardiographic, and angiographic data were collected. The primary endpoint was 30-day all-cause mortality. A weighted score comprising of pre-ST-MCS variables independently associated with 30-day all-cause mortality was derived and internally validated. RESULTS: A total of 159 patients (mean age, 61 years; 78% male) were included. Thirty-day all-cause mortality was 49%. Multivariable analysis resulted in four independent predictors of 30-day all-cause mortality: age, lactate, SCAI CS classification, and acute kidney injury. The model had good calibration and discrimination (area under the receiver operating characteristics curve 0.80). A predictive score (ranging 0-4) comprised of age ≥ 60 years, pre-ST-MCS lactate ≥2.5 mmol/L, AKI at time of ST-MCS implementation, and SCAI CS stage E effectively risk stratified our patient population. CONCLUSION: The ACS-MCS score is a simple and practical predictive score to risk-stratify CS secondary to ACS patients based on their mortality risk. Effective mortality risk assessment for ACS-CS patients could have implications on patient selection for available therapeutic strategy options.

Smartphone ECG Monitoring System Helps Lower Emergency Room and Clinic Visits in Post-Atrial Fibrillation Ablation Patients.

AIM: To evaluate the effectiveness of using a smartphone-based electrocardiography (ECG) monitoring device (ECG Check) on the frequency of clinic or emergency room visits in patients who underwent ablation of atrial fibrillation (AF). METHODS: Two groups of patients were identified and compared: The conventional monitoring group (CM group) included patients who were prescribed conventional event monitoring or Holter monitoring systems. The ECG Check group (EC group) included patients who were prescribed the ECG Check device for continuous monitoring in addition to conventional event monitoring. The primary outcome was the number of patient visits to clinic or emergency room. The feasibility, accuracy, and detection rate of mobile ECG Check were also evaluated. RESULTS: Ninety patients were studied (mean age: 66.2 ± 11 years, 64 males, mean CHA2DS2-VASc score: 2.6 ± 2). In the EC group, forty-five patients sent an average of 52.8 ± 6 ECG records for either routine monitoring or symptoms of potential AF during the follow-up period. The rhythm strips identified sinus rhythm (84.7%), sinus tachycardia (8.4%), AF (4.2%), and atrial flutter (0.9%). Forty-two EC transmissions (1.8%) were uninterpretable. Six patients (13%) in the EC group were seen in the clinic or emergency room over a 100-day study period versus 16 (33%) in the standard care arm (P value < 0.001). CONCLUSIONS: Use of smartphone-based ECG monitoring led to a significant reduction in AF-related visits to clinic or emergency department in the postablation period.

High-Power Radiofrequency Catheter Ablation of Atrial Fibrillation: Using Late Gadolinium Enhancement Magnetic Resonance Imaging as a Novel Index of Esophageal Injury.

OBJECTIVES: This study retrospectively evaluated the feasibility and esophageal thermal injury (ETI) patterns of high-power short-duration (HPSD) radiofrequency atrial fibrillation (AF) ablation. BACKGROUND: ETI following AF ablation can lead to serious complications. Little consensus exists on the optimal radiofrequency power setting or on the optimal strategy to assess ETI. METHODS: A total of 687 patients undergoing first-time AF ablation with either HPSD ablation (50 W for 5 s, n = 574) or low-power long-duration ablation (LPLD, ≤35 W for 10 to 30 s, n = 113) were analyzed. ETI was assessed by late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) within 24 h post-ablation. Patients with moderate or severe esophageal LGE had a follow-up MRI within 24 h to 1 week, and esophagogastroduodenoscopies were performed when significant gastrointestinal symptoms or persistent LGE on repeat MRI was present. AF recurrence adjusted for potential confounders was analyzed. RESULTS: The average age was 69.0 ± 11.8 years in the group undergoing HPSD ablation versus 68.3 ± 11.6 years in the LPLD group (p = 0.554), with 67.1% versus 59.3% male (p = 0.111). Esophageal LGE patterns were similar (64.8% vs. 57.5% none, 21.0% vs. 28.3% mild, 11.5% vs. 11.5% moderate, 2.8% vs. 2.7% severe for HPSD vs. LPLD, respectively; p = 0.370) with no atrioesophageal fistulas. Mean procedure length was significantly shorter in the HPSD group (149 ± 65 min vs. 251 ± 101 min; p < 0.001). AF recurrence rates were similar in the 2 groups for the mean 2.5-year follow-up period (adjusted, 42% vs. 41%; p = 0.571). CONCLUSIONS: HPSD ablation results in similar ETI patterns, as assessed by same-day LGE MRI, compared with the LPLD setting but with significantly shorter procedure times. Recurrence rates at 2.5-year follow-up are similar.

Atrial Fibrosis by Late Gadolinium Enhancement Magnetic Resonance Imaging and Catheter Ablation of Atrial Fibrillation: 5-Year Follow-Up Data.

Background Late gadolinium enhancement magnetic resonance imaging is an effective tool for assessment of atrial fibrosis. The degree of left atrial fibrosis is a good predictor of atrial fibrillation ( AF ) ablation success at 1 year, but the association between left atrial fibrosis and long-term ablation success has not been studied. Methods and Results Late gadolinium enhancement magnetic resonance images of sufficient quality to quantify atrial fibrosis were obtained before the first AF ablation in 308 consecutive patients. Left atrial fibrosis was classified in 4 Utah stages (I, 0-10%; II , 10-20%; III , 20-30%; and IV , >30%). Patients were followed up for up to 5 years until the time of first arrhythmia recurrence or second ablation. A total of 308 patients were included; the mean age was 64.5±12.1 years, and 63.4% were men. During follow-up, 157 patients experienced an arrhythmia recurrence and 106 patients underwent a repeated ablation. A graded effect was observed in which patients with more advanced atrial fibrosis were more likely to experience recurrent AF (hazard ratio for stage IV versus stage I, 2.73; 95% confidence interval, 1.57-4.75) and undergo a repeated ablation (proportional odds ratio for stage IV versus stage I, 5.19; 95% confidence interval, 2.12-12.69). Conclusions The degree of left atrial fibrosis predicts the success of AF ablation at up to 5 years follow-up. In patients with advanced atrial fibrosis, AF ablation is associated with a high procedural failure rate.

Increases in Heart Rate Variability Signal Improved Outcomes in Rapid Response Team Consultations: A Cohort Study.

BACKGROUND: Reduced heart rate variability (HRV) indicates dominance of the sympathetic system and a state of "physiologic stress." We postulated that, in patients with critical illness, increases in HRV might signal successful resuscitation and improved prognosis. METHODS: We carried out a prospective observational study of HRV on all patients referred to the rapid response team (RRT) and correlated with serial vital signs, lactate clearance, ICU admission, and mortality. RESULTS: Ninety-one patients were studied. Significantly higher HRV was observed in patients who achieved physiological stability and did not need ICU admission: ASDNN 19 versus 34.5, p=0.032; rMSSD 13.5 versus 25, p=0.046; mean VLF 9.4 versus 17, p=0.021; mean LF 5.8 versus 12.4, p=0.018; and mean HF 4.7 versus 10.5, p=0.017. ROC curves confirmed the change in very low frequencies at 2 hours as a strong predictor for ICU admission with an AUC of 0.772 (95% CI 0.633, 0.911, p=0.001) and a cutoff value of -0.65 associated with a sensitivity of 78.6% and a specificity of 61%. CONCLUSIONS: Reduced HRV, specifically VLF, appears closely related to greater severity of critical illness, identifies unsuccessful resuscitation, and can be used to identify consultations that need early ICU admission.

The incidence of increased ICP in ICU patients with non-traumatic coma as diagnosed by ONSD and CT: a prospective cohort study.

BACKGROUND: Unexplained coma after critical illness can be multifactorial. We evaluated the diagnostic ability of bedside Optic Nerve Sheath Diameter [ONSD] as a screening test for non-traumatic radiographic cerebral edema. METHODS: In a prospective study, mixed medical-surgical intensive care units [ICU] patients with non-traumatic coma [GCS < 9] underwent bedside ultrasonographic ONSD measurements. Non-traumatic radiographic cerebral edema [NTRCE] was defined as > 5 mm midline shift, cisternal, sulcal effacement, or hydrocephalus on CT. RESULTS: NTRCE was identified in 31 of 102 patients [30.4 %]. The area under the ROC curve for detecting radiographic edema by ONSD was 0.785 [95 % CI 0.695-0.874, p <0.001]. ONSD diameter of 0.57 cm was found to be the best cutoff threshold with a sensitivity 84 % and specificity 71 %, AUC 0.785 [95 % CI 0.695-0.874, p <0.001]. Using ONSD as a bedside test increased the post-test odds ratio [OR] for NTRCE by 2.89 times [positive likelihood ratio], whereas post-test OR for NTRCE decreased markedly given a negative ONSD test [ONSD measurement less than 0.57 cm]; negative likelihood ratio 0.22. CONCLUSIONS: The use of ONSD as a bedside test in patients with non-traumatic coma has diagnostic value in identifying patients with non-traumatic radiographic cerebral edema.

Deletion of low molecular weight protein tyrosine phosphatase (Acp1) protects against stress-induced cardiomyopathy.

The low molecular weight protein tyrosine phosphatase (LMPTP), encoded by the ACP1 gene, is a ubiquitously expressed phosphatase whose in vivo function in the heart and in cardiac diseases remains unknown. To investigate the in vivo role of LMPTP in cardiac function, we generated mice with genetic inactivation of the Acp1 locus and studied their response to long-term pressure overload. Acp1(-/-) mice develop normally and ageing mice do not show pathology in major tissues under basal conditions. However, Acp1(-/-) mice are strikingly resistant to pressure overload hypertrophy and heart failure. Lmptp expression is high in the embryonic mouse heart, decreased in the postnatal stage, and increased in the adult mouse failing heart. We also show that LMPTP expression increases in end-stage heart failure in humans. Consistent with their protected phenotype, Acp1(-/-) mice subjected to pressure overload hypertrophy have attenuated fibrosis and decreased expression of fibrotic genes. Transcriptional profiling and analysis of molecular signalling show that the resistance of Acp1(-/-) mice to pathological cardiac stress correlates with marginal re-expression of fetal cardiac genes, increased insulin receptor beta phosphorylation, as well as PKA and ephrin receptor expression, and inactivation of the CaMKIIδ pathway. Our data show that ablation of Lmptp inhibits pathological cardiac remodelling and suggest that inhibition of LMPTP may be of therapeutic relevance for the treatment of human heart failure.

Control of histone H3 phosphorylation by CaMKIIδ in response to haemodynamic cardiac stress.

Heart failure is associated with the reactivation of a fetal cardiac gene programme that has become a hallmark of cardiac hypertrophy and maladaptive ventricular remodelling, yet the mechanisms that regulate this transcriptional reprogramming are not fully understood. Using mice with genetic ablation of calcium/calmodulin-dependent protein kinase II δ (CaMKIIδ), which are resistant to pathological cardiac stress, we show that CaMKIIδ regulates the phosphorylation of histone H3 at serine-10 during pressure overload hypertrophy. H3 S10 phosphorylation is strongly increased in the adult mouse heart in the early phase of cardiac hypertrophy and remains detectable during cardiac decompensation. This response correlates with up-regulation of CaMKIIδ and increased expression of transcriptional drivers of pathological cardiac hypertrophy and of fetal cardiac genes. Similar changes are detected in patients with end-stage heart failure, where CaMKIIδ specifically interacts with phospho-H3. Robust H3 phosphorylation is detected in both adult ventricular myocytes and in non-cardiac cells in the stressed myocardium, and these signals are abolished in CaMKIIδ-deficient mice after pressure overload. Mechanistically, fetal cardiac genes are activated by increased recruitment of CaMKIIδ and enhanced H3 phosphorylation at hypertrophic promoter regions, both in mice and in human failing hearts, and this response is blunted in CaMKIIδ-deficient mice under stress. We also document that the chaperone protein 14-3-3 binds phosphorylated H3 in response to stress, allowing proper elongation of fetal cardiac genes by RNA polymerase II (RNAPII), as well as elongation of transcription factors regulating cardiac hypertrophy. These processes are impaired in CaMKIIδ-KO mice after pathological stress. The findings reveal a novel in vivo function of CaMKIIδ in regulating H3 phosphorylation and suggest a novel epigenetic mechanism by which CaMKIIδ controls cardiac hypertrophy.