Cardiac Resynchronization Therapy for the Treatment of Mild Heart Failure: A Review of the Clinical Data

Cardiac resynchronization therapy (CRT) was originally established as an effective treatment for patients with systolic heart failure (HF) with NewYork Heart Association ClassIII–IV symptoms, reduced left ventricular ejection fraction and prolonged QRS duration ≥120 ms. Subsequent studies expanded the role of CRT to the treatment of patients with mildly symptomatic HF as these patients experienced similar improvement in clinical symptoms and reverse remodeling of the left ventricle. These clinical trial results were incorporated into the 2013 guidelines on cardiac pacing and CRT from the European Society of Cardiology and the 2012 American College of Cardiology Foundation/American Heart Association/Heart Rhythm Society Focused Update on Device-based Therapy of Cardiac Rhythm Abnormalities. Additional data from careful post hoc and substudy analyses as well as long-term follow-up of the original study cohorts have been performed. These results attempt to identify subgroups more likely to benefit from CRT, to define the association between response and QRS morphology/duration and to demonstrate the sustained benefit of CRT in this population. More importantly, these results highlight that patients with mildly symptomatic HF who respond to CRT not only have improvement in clinical symptoms but also receive a therapy that may prevent or delay progression of HF. A review of the clinical trials in mildly symptomatic HF and the results of subsequent post hoc analysis are summarized herein.<div><br></div><div>DOI: 10.4103/2352-4197.208455<br></div><div><br></div><div><div>How to cite this article:</div><div>Phelan TP, Mackall JA. Cardiac resynchronization therapy for the treatment of mild heart failure: A review of the clinical data. Int J Heart Rhythm 2017;2:5-12</div></div><div><br></div><div><br></div><div><br></div><div><br></div

Acute Pulmonary Edema Associated With Direct Current Cardioversion in a Structurally Normal Heart

The transthoracic application of synchronized direct current cardioversion (DCC) is widely used to terminate atrial fibrillation, atrial flutter, and other supraventricular tachyarrhythmia. DCC is a highly effective method for acute restoration of sinus rhythm. Although DCC is a relatively safe and frequently performed procedure, data on potential side effects are very rarely reported in the literature. The most serious complications associated with DCC are thromboembolism and intracranial hemorrhage. The true incidence of postcardioversion pulmonary edema is not known, but it is estimated to occur in 1%to 3% of patients, particularly those with coexistent heart disease. We report on a patient with a structurally normal heart who developed acute pulmonary edema after undergoing DCC. The patient had no evidence of myocardial injury according to an electrocardiogram and cardiac biomarkers. The patient was treated with intravenous diuretics. After 4 days, the pulmonary edema resolved

Symptomatic Repetitive Right Ventricular Outflow Tract Ventricular Tachycardia in Pregnancy and Postpartum

Idiopathic ventricular tachycardias, which occur in patients without structural heart disease, are a common entity, representing up to 10% of all ventricular tachycardias evaluated by cardiac electrophysiology services. Pregnancy can increase the incidence of various cardiac arrhythmias. Factors that can potentially promote arrhythmias in pregnancy include the effects of hormones, changes in autonomic tone, hemodynamic perturbations, hypokalemia, and underlying heart disease. Ventricular arrhythmias in pregnancy are repetitive monomorphic ventricular premature complexes and couplets that frequently originate at the right ventricular outflow tract. New onset symptomatic repetitive right ventricular outflow tract ventricular tachycardia during pregnancy has been inadequately reported in the literature. We present a case of symptomatic repetitive right ventricular outflow tract tachycardia that started during pregnancy and continued in the postpartum period, requiring curative treatment with electrophysiology study and radiofrequency ablation

Adipogenic Signaling Promotes Arrhythmia Substrates before Structural Abnormalities in TMEM43 ARVC

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder of desmosomal and structural proteins that is characterized by fibro-fatty infiltrate in the ventricles and fatal arrhythmia that can occur early before significant structural abnormalities. Most ARVC mutations interfere with β-catenin–dependent transcription that enhances adipogenesis; however, the mechanistic pathway to arrhythmogenesis is not clear. We hypothesized that adipogenic conditions play an important role in the formation of arrhythmia substrates in ARVC. Cardiac myocyte monolayers co-cultured for 2–4 days with mesenchymal stem cells (MSC) were derived from human-induced pluripotent stem cells with the ARVC5 TMEM43 p.Ser358Leu mutation. The TMEM43 mutation in myocyte co-cultures alone had no significant effect on impulse conduction velocity (CV) or APD. In contrast, when co-cultures were exposed to pro-adipogenic factors for 2–4 days, CV and APD were significantly reduced compared to controls by 49% and 31%, respectively without evidence of adipogenesis. Additionally, these arrhythmia substrates coincided with a significant reduction in IGF-1 expression in MSCs and were mitigated by IGF-1 treatment. These findings suggest that the onset of enhanced adipogenic signaling may be a mechanism of early arrhythmogenesis, which could lead to personalized treatment for arrhythmias associated with TMEM43 and other ARVC mutations

Impact of catheter ablation in patients with atrial flutter and concurrent heart failure

Background: No studies assessed impact of atrial flutter (AFL) ablation on outcomes in patients with AFL and concurrent heart failure (HF). Objectives: To assess the effect of AFL ablation on mortality and HF readmissions in patients with AFL and HF. Methods: This retrospective cohort study identified 15,952 patients with AFL and HF from the 2016-17 Nationwide Readmissions Database. The primary outcome was a composite of all-cause mortality and/or HF readmission at 1 year. Secondary outcomes included HF readmission, all-cause mortality, and atrial fibrillation (AF) readmission at 1 year. Propensity score match (1:2) algorithm was used to adjust for confounders. Cox proportional hazard regression was used to generate hazard ratios. Results: Of the 15,952 patients, 9889 had heart failure with reduced ejection fraction (HFrEF) and 6063 had heart failure with preserved ejection fraction (HFpEF). In the matched HFrEF cohort (n = 5421), the primary outcome was significantly lower in patients undergoing ablation (HR 0.72, 95% CI 0.61-0.85, \u3c .001). HF readmission (HR 0.73, 95% CI 0.61-0.89, = .001), all-cause mortality (HR 0.62, 95% CI 0.46-0.85, = .003), and AF readmission (HR 0.63, 95% CI 0.48-0.82, = .001) were also significantly reduced. In the matched HFpEF cohort (n = 2439), the primary outcome was lower in the group receiving ablation but was not statistically significant (HR 0.80, 95% CI 0.63-1.01, = .065). Conclusion: In patients with AFL and HFrEF, AFL ablation was associated with lower mortality and HF readmissions at 1 year. Patients with AFL and HFpEF did not show a similar significant reduction in the primary outcome

Incidence and risk factors associated with bleeding and thrombosis following chimeric antigen receptor T-cell therapy

Abstract Bleeding and thrombotic events are an emerging toxicity associated with chimeric antigen receptor (CAR) therapies. To determine their incidence, we retrospectively analyzed consecutive adult patients (N = 127) with large B-cell lymphoma (LBCL) or B-cell acute lymphoblastic leukemia (B-ALL) treated from 2017 through 2020 with axicabtagene ciloleucel (axi-cel; n = 89) or a bispecific CD19/CD22 CAR (n = 38). Twelve (9.4%) and 8 (6.3%) patients developed bleeding and thrombosis within the first 3 months, respectively. In the axi-cel subgroup, these occurred in 11.2% and 6.7%, respectively. Bleeding occurred between days 8 and 30 (median, 17.5) and thrombosis between days 2 and 91 (median, 29). Bleeding sites included genitourinary, soft tissue, intracranial, gastrointestinal, and pulmonary and were associated with features of consumptive coagulopathy. On univariate analysis, patients with bleeding were older, had lower baseline platelets (86 × 103/μL vs 178 × 103/μL; P < .01), lower platelet and fibrinogen nadirs , and elevated lactate dehydrogenase. Immune effector cell (IEC)–associated neurotoxicity syndrome (ICANS) grade ≥3 was associated with increased bleeding (50% vs 15%; P = .01), thrombosis (50% vs 16%; P = .04), prothrombin time prolongation, hypofibrinogenemia, and elevated D-dimer. Low pretreatment platelet counts were associated with bleeding in a multivariate logistic regression model. Patients with thrombocytopenia or severe ICANS are at increased risk of bleeding and should be closely monitored, particularly within the first month after CAR therapy. Future studies in larger cohorts should assess risk factors for systemic coagulopathies in CAR T therapy, including their association with neurotoxicity