Treatment of RAF1-Related Obstructive Hypertrophic Cardiomyopathy by MEK Inhibition Using Trametinib.

RASopathies cause nonsarcomeric hypertrophic cardiomyopathy via dysregulated signaling through RAS and upregulated mitogen-activated protein kinase activity. We provide the first report of the successful treatment of an adult with RAF1-associated hypertrophic cardiomyopathy using trametinib, a MEK inhibitor.

Patients with non-ischemic cardiomyopathy and mid-wall striae have similar arrhythmic outcomes as ischemic cardiomyopathy.

PURPOSE: While implantable cardioverter-defibrillator (ICD) therapy provides clear benefit in patients with ischemic cardiomyopathy (ICM), this is less clear in patients with non-ischemic cardiomyopathy (NICM). Mid-wall striae (MWS) fibrosis is an established cardiovascular magnetic resonance (CMR) risk marker observed in patients with NICM. We evaluated whether patients with NICM and MWS have similar risk of arrhythmia-related cardiovascular events as patients with ICM. METHODS: We studied a cohort of patients undergoing CMR. The presence of MWS was adjudicated by experienced physicians. The primary outcome was a composite of implantable cardioverter-defibrillator (ICD) implant, hospitalization for ventricular tachycardia, resuscitated cardiac arrest, or sudden cardiac death. Propensity-matched analysis was performed to compare outcomes for patients NICM with MWS and ICM. RESULTS: A total of 1,732 patients were studied, 972 NICM (706 without MWS, 266 with MWS) and 760 ICM. NICM patients with MWS were more likely to experience the primary outcome versus those without MWS (unadjusted subdistribution hazard ratio (subHR) 2.26, 95% confidence interval [CI] 1.51-3.41) with no difference versus ICM patients (unadjusted subHR 1.32, 95% CI 0.93-1.86). Similar results were seen in a propensity-matched population (adjusted subHR 1.11, 95% CI 0.63-1.98, p = 0.711). CONCLUSION: Patients with NICM and MWS demonstrate significantly higher arrhythmic risk compared to NICM without MWS. After adjustment, the arrhythmia risk of patients with NICM and MWS was similar to patients with ICM. Accordingly, physicians could consider the presence of MWS when making clinical decisions regarding arrhythmia risk management in patients with NICM.

Paradigm Shifts in Cardiac Pacing: Where Have We Been and What Lies Ahead?

The history of cardiac pacing dates back to the 1930s with externalized pacing and has evolved to incorporate transvenous, multi-lead, or even leadless devices. Annual implantation rates of cardiac implantable electronic devices have increased since the introduction of the implantable system, likely related to expanding indications, and increasing global life expectancy and aging demographics. Here, we summarize the relevant literature on cardiac pacing to demonstrate the enormous impact it has had within the field of cardiology. Further, we look forward to the future of cardiac pacing, including conduction system pacing and leadless pacing strategies.

Clinical Updates in Cardiac Pacing-The Future Is Bright.

The history of cardiac pacing has been defined by many innovation milestones starting in the early 1960s [...].

Cardioneuroablation for vasovagal syncope: A systematic review and meta-analysis.

BACKGROUND: Cardioneuroablation (CNA) has emerged as promising therapy for patients with refractory vasovagal syncope (VVS). OBJECTIVE: The purpose of this study was to provide a freedom from syncope estimate for CNA, including subgroup analysis by method and target of ablation. METHODS: A systematic search was performed in MEDLINE and EMBASE according to the PRISMA guidelines until February 14, 2022. Observational studies and clinical trials reporting freedom from syncope were included. Meta-analysis was performed with a random-effects model. RESULTS: A total of 465 patients were included across 14 studies (mean age 39.8 ± 4.0 year; 53.5% female). Different techniques were used to guide CNA: 50 patients (10.8%) by mapping fractionated electrograms, 73 (15.7%) with the spectral method, 210 (45.2%) with high-frequency stimulation, 73 (15.7%) with a purely anatomically guided method, and 59 (12.6%) with a combination. The target was biatrial in 168 patients (36.1%), left atrium only in 259 (55.7%), and right atrium only in 38 (8.2%). The freedom from syncope was 91.9% (95% confidence interval [CI] 88.1%-94.6%; I2 = 6.9%; P = .376). CNA limited to right atrial ablation was associated with a significant lower freedom from syncope (81.5%; 95% CI 51.9%-94.7%; P <.0001) vs left atrial ablation only (94.0%; 95% CI 88.6%--6.9%) and biatrial ablation (92.7%; 95% CI 86.8%-96.1%). Subgroup analysis according to the technique used to identify ganglionated plexi did not show any significant difference in freedom from syncope (P = .206). CONCLUSION: This meta-analysis suggests a high freedom from syncope after CNA in VVS. Well-designed, double-blind, multicenter, sham-controlled randomized clinical trials are needed to provide evidence for future guidelines.

Management of vasovagal syncope.

Vasovagal syncope (VVS) is a very common form of fainting. Treatment begins with patient education about the mechanism of fainting, and the non-lethal nature of vasovagal syncope. In this article, we review several non-pharmacological approaches that form the foundation of our current treatments. These include increases in dietary salt and water intake, the use of compression garments, physical counter-maneuvers and tilt-training. When these approaches are inadequate, medications can sometimes be effective. While the evidence base for the pharmacological treatment of VVS is modest, recent trial data have found drugs to be useful in placebo-controlled randomized trials. For select patients, and those patients more refractory to medications, procedural treatments may be an option. In this review, we discuss the current state of evidence for the non-pharmacological and pharmacological treatments for VVS, as well as some novel, emerging therapies for VVS.

Stroke risk and atrial mechanical dysfunction in cardiac amyloidosis.

Amyloidosis is associated with poor prognosis, and patients with cardiac involvement have especially poor outcomes. Cardiac amyloidosis leads to higher rates of atrial arrhythmia and an increased risk of intracardiac thrombus formation. However, atrial mechanical dysfunction due to protein deposition in amyloidosis may lead to thrombus formation in the absence of atrial arrhythmia. We present a 42-year-old male patient with familial transthyretin amyloidosis who suffered an embolic stroke that originated from a left atrial appendage thrombus in the absence of any documented atrial fibrillation. This case highlights atrial mechanical dysfunction in patients with cardiac amyloidosis and the need to better stratify thrombotic risk in this population with integration of echocardiographic parameters and transesophageal echocardiography.

Early Versus Standard Discharge After Transcatheter Aortic Valve Replacement: A Systematic Review and Meta-Analysis.

OBJECTIVES: This study sought to assess the clinical outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) with early discharge (ED) versus standard discharge (SD) pathways. BACKGROUND: Minimalist approaches for TAVR have been developed targeting different aspects of the procedure such as local anesthesia or sedation, intraprocedural imaging, vascular access, post-operative monitoring and care, and discharge planning. Their incorporation into routine clinical practice aims to reduce length of hospital stay and health care cost utilization without adversely affecting outcomes when compared with standard approaches. METHODS: The authors conducted a search of MEDLINE and EMBASE to identify studies that investigated ED (≤3 days) versus SD in TAVR patients. Random-effects meta-analyses were used to estimate the effect of ED compared with SD with regard to 30-day mortality after discharge, 30-day readmission rate, and need for permanent pacemaker implantation (PPI) following discharge. RESULTS: Eight studies including 1,775 participants (ED, n = 642) fulfilled the inclusion criteria. The mean age was 82.4 years and STS score was 6.7. Meta-analyses evaluating discharge to 30-day mortality (odds ratio [OR]: 0.65; 95% confidence interval [CI]: 0.23 to 1.82; I2 = 0%) and discharge to 30-day new PPI (OR: 1.61; 95% CI: 0.19 to 13.71; I2 = 40%) showed no significant difference in an ED compared with a SD strategy. Notably, ED patients were less likely to be readmitted after ED when compared with SD patients (OR: 0.63; 95% CI: 0.41 to 0.98; p = 0.04, I2 = 0%). CONCLUSIONS: ED following uncomplicated TAVR is safe in terms of discharge to 30-day mortality or need for PPI following discharge. Moreover, ED patients experienced a lower rate of readmissions. These data support the safety of programs aiming an ED pathway in selected TAVR patients. Institutional protocols with the input from different members of the multidisciplinary heart team should be devised to optimize discharge processes to improve health care resource utilization.

Cardiac resynchronization is pro-arrhythmic in the absence of reverse ventricular remodelling: a systematic review and meta-analysis.

Aims: Cardiac resynchronization therapy (CRT) has been shown to reduce mortality and heart failure (HF) hospitalization but its effects on the rate of ventricular arrhythmias (VAs) appears to be neutral. We hypothesize that CRT with LV epicardial stimulation is inherently pro-arrhythmic and increases VA rates in the absence of reverse ventricular remodelling while conferring an anti-arrhythmic effect in mechanical responders. Methods and results: In this systematic review and meta-analysis, we considered retrospective cohort, prospective cohort, and randomized controlled trials comparing VA rates between cardiac resynchronization therapy-defibrillator (CRT-D) non-responders, CRT-D responders and those with implantable cardioverter-defibrillator (ICD) only. Studies were eligible if they defined CRT-D responders using a discrete left ventricular volumetric value as assessed by any imaging modality. Studies were identified through searching electronic databases from their inception to July 2017. We identified 2579 citations, of which 23 full-text articles were eligible for final analysis. Our results demonstrated that CRT-D responders were less likely to experience VA than CRT-D non-responders, relative risk (RR) 0.49 [95% confidence interval (CI) 0.41-0.58, P < 0.01] and also less than patients with ICD only: RR 0.59 (95% CI 0.50-0.69, P < 0.01). However, CRT-D mechanical non-responders had a greater likelihood of VA compared with ICD only, RR 0.76 (95% CI 0.63-0.92, P = 0.004). Conclusion: CRT-D non-responders experienced more VA than CRT-D responders and also more than those with ICD only, suggesting that CRT with LV epicardial stimulation may be inherently pro-arrhythmic in the absence of reverse remodelling.

Unique ECG Findings in Acute Pulmonary Embolism: STE with Reciprocal Changes and Pathologic Q Wave.

A 68-year-old male presented to the emergency department with retrosternal chest pain, presyncope, and then a pulseless electrical activity cardiac arrest. An ECG prior to his arrest revealed ST elevations in leads V1-V3, Q waves in lead V2, and reciprocal ST depressions in the lateral and inferior leads. He received thrombolytic therapy for a presumptive diagnosis of ST elevation myocardial infarction. Return of spontaneous circulation was achieved and he underwent a coronary angiogram. No critical disease was found and his left ventriculogram showed normal contraction. His ongoing metabolic acidosis and dependence on an intra-aortic balloon pump, despite adequate cardiac output, prompted a CT pulmonary angiogram which showed multiple segmental filling defects. He was treated for a pulmonary embolism and was discharged 5 days later. Acute pulmonary embolism (APE) has variable clinical presentations. To our knowledge, this is the first case report of an APE presenting with these ECG findings suggestive of myocardial ischemia. In this case report, we discuss the underlying physiological mechanisms responsible and offer management suggestions for emergency department and critical care physicians to better expedite the treatment of APE mimicking acute coronary syndrome on ECG.