Ventricular arrhythmia (VA) in structurally normal hearts can be broadly considered under non–life-threatening monomorphic and life-threatening polymorphic rhythms. Monomorphic VA is classified on ...the basis of site of origin in the heart, and the most common areas are the ventricular outflow tracts and left ventricular fascicles. The morphology of the QRS complexes on electrocardiogram is an excellent tool to identify the site of origin of the rhythm. Although these arrhythmias are common and generally carry an excellent prognosis, rare sudden death events have been reported. Very frequent ventricular ectopy may also result in a cardiomyopathy in a minority of patients. Suppression of VA may be achieved using calcium-channel blockers, beta-adrenergic blockers, and class I or III antiarrhythmic drugs. Radiofrequency ablation has emerged as an excellent option to eliminate these arrhythmias, although certain foci including aortic cusps and epicardium may be technically challenging. Polymorphic ventricular tachycardia (VT) is rare and generally occurs in patients with genetic ion channel disorders including long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and short QT syndrome. Unlike monomorphic VT, these arrhythmic syndromes are associated with sudden death. While the cardiac gross morphology is normal, suggesting a structurally normal heart, abnormalities exist at the molecular level and predispose them to arrhythmias. Another fascinating area, idiopathic ventricular fibrillation and early repolarization syndrome, are undergoing research for a genetic basis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
Treatment of Atrial Fibrillation Prystowsky, Eric N; Padanilam, Benzy J; Fogel, Richard I
JAMA : the journal of the American Medical Association,
07/2015, Volume:
314, Issue:
3
Journal Article
Peer reviewed
IMPORTANCE: Atrial fibrillation is a common arrhythmia that affects more than 2.5 million people in the United States and causes substantial morbidity and mortality, especially regarding the ...increased risk of stroke. OBJECTIVE: To summarize atrial fibrillation treatment exclusive of stroke prevention. EVIDENCE REVIEW: An Ovid MEDLINE comprehensive literature search was performed on atrial fibrillation therapy excluding anticoagulation and emphasizing studies published within the last 5 years through April 2015 (N = 5044 references). The 2014 atrial fibrillation guideline from the American Heart Association, the American College of Cardiology, and the Heart Rhythm Society also was reviewed. FINDINGS: Reversible causes of atrial fibrillation should be identified. Risk factor modification, including weight loss and treatment of hypertension, diabetes, and obstructive sleep apnea can reduce atrial fibrillation episodes. Appropriate anticoagulation is necessary for patients at substantial stroke risk regardless of rate or rhythm treatment strategy. Sinus rhythm is often needed to control symptoms; however, an alternative strategy for atrial fibrillation is appropriate rate control. Rate control is safe in older patients (those who are about age ≥65 years) followed up for a few years, but no such safety data exist for patients younger than 60 years or for those followed up for longer periods. Thus, selection of therapy is individualized, taking into account present and future medical problems for the patient. Choice of an antiarrhythmic drug is based on safety first vs efficacy. Catheter ablation is an effective nonpharmacological alternative that is often, but not always, the second-line treatment. Reduction of the frequency and duration of atrial fibrillation episodes that result in a significant improvement in quality of life is a good marker of drug treatment success and complete elimination of atrial fibrillation is not required in many patients. Rate control is usually achieved with a β-blocker or non–dihydropyridine calcium channel blockers. It is important to assess adequate rate control during both rest and activity. If the ventricular rate goes uncontrolled for a prolonged period, tachycardia-mediated cardiomyopathy can occur. CONCLUSIONS AND RELEVANCE: Therapy for atrial fibrillation includes prevention and modification of inciting causes and appropriate anticoagulation. Rate control is necessary for all patients. Maintenance of sinus rhythm with drugs or catheter ablation should be considered based on the individual needs of each patient.
Reducing expression of the fetal hemoglobin (HbF) repressor BCL11A leads to a simultaneous increase in γ-globin expression and reduction in β-globin expression. Thus, there is interest in targeting ...BCL11A as a treatment for β-hemoglobinopathies, including sickle cell disease (SCD) and β-thalassemia. Here, we found that using optimized shRNAs embedded within an miRNA (shRNAmiR) architecture to achieve ubiquitous knockdown of BCL11A profoundly impaired long-term engraftment of both human and mouse hematopoietic stem cells (HSCs) despite a reduction in nonspecific cellular toxicities. BCL11A knockdown was associated with a substantial increase in S/G2-phase human HSCs after engraftment into immunodeficient (NSG) mice, a phenotype that is associated with HSC exhaustion. Lineage-specific, shRNAmiR-mediated suppression of BCL11A in erythroid cells led to stable long-term engraftment of gene-modified cells. Transduced primary normal or SCD human HSCs expressing the lineage-specific BCL11A shRNAmiR gave rise to erythroid cells with up to 90% reduction of BCL11A protein. These erythrocytes demonstrated 60%-70% γ-chain expression (vs. < 10% for negative control) and a corresponding increase in HbF. Transplantation of gene-modified murine HSCs from Berkeley sickle cell mice led to a substantial improvement of sickle-associated hemolytic anemia and reticulocytosis, key pathophysiological biomarkers of SCD. These data form the basis for a clinical trial application for treating sickle cell disease.
Importance Infection with SARS-CoV-2, which causes COVID-19, is associated with adverse maternal outcomes. While it is known that severity of COVID-19 varies by viral strain, the extent to which this ...variation is reflected in adverse maternal outcomes, including nonpulmonary maternal outcomes, is not well characterized. Objective To evaluate the associations of SARS-CoV-2 infection with severe maternal morbidities (SMM) in pregnant patients delivering during 4 pandemic periods characterized by predominant viral strains. Design, Setting, and Participants This retrospective cohort study included patients delivering in a multicenter, geographically diverse US health system between March 2020 and January 2022. Individuals with SARS-CoV-2 infection were propensity-matched with as many as 4 individuals without evidence of infection based on demographic and clinical variables during 4 time periods based on the dominant strain of SARS-CoV-2: March to December 2020 (wild type); January to June 2021 (Alpha B.1.1.7); July to November 2021 (Delta B.1.617.2); and December 2021 to January 2022 (Omicron B.1.1.529). Data were analyzed from October 2021 to June 2022. Exposures Positive SARS-CoV-2 nucleic acid amplification test result during the delivery encounter. Main Outcomes and Measures The primary outcome was any SMM event, as defined by the US Centers for Disease Control and Prevention, during hospitalization for delivery. Secondary outcomes were number of SMM, respiratory SMM, nonrespiratory SMM, and nontransfusion SMM events. Results Over all time periods, there were 3129 patients with SARS-CoV-2, with a median (IQR) age of 29.1 (24.6-33.2) years. They were propensity matched with a total of 12 504 patients without SARS-CoV-2, with a median (IQR) age of 29.2 (24.7-33.2) years. Patients with SARS-CoV-2 infection had significantly higher rates of SMM events than those without in all time periods, except during Omicron. While the risk of any SMM associated with SARS-CoV-2 infection was increased for the wild-type strain (odds ratio OR, 2.74 95% CI, 1.85-4.03) and Alpha variant (OR, 2.57 95% CI, 1.69-4.01), the risk during the Delta period was higher (OR, 7.69 95% CI, 5.19-11.54;Pfor trend < .001). The findings were similar for respiratory complications, nonrespiratory complications, and nontransfusion outcomes. For example, the risk of nonrespiratory SMM events for patients with vs without SARS-CoV-2 infection were similar for the wild-type strain (OR, 2.16 95% CI, 1.40-3.27) and Alpha variant (OR, 1.96 95% CI, 1.20-3.12), highest for the Delta variant (OR, 4.65 95% CI, 2.97-7.29), and not significantly higher in the Omicron period (OR, 1.21 95% CI, 0.67-2.08;Pfor trend < .001). Conclusions and Relevance This cohort study found that the SARS-CoV-2 Delta variant was associated with higher rates of SMM events compared with other strains. Given the potential of new strains, these findings underscore the importance of preventive measures.
...patients who undergo ICD placement late in the day followed by discharge the next morning may receive a comparable level of care. Similar to same-day discharge after percutaneous coronary ...intervention, same-day discharge after ICD placement may lead to greater patient satisfaction, increased bed availability for patients with greater clinical need, and cost savings without adversely affecting readmission rates (3).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
BACKGROUND—Although cardiac resynchronization therapy (CRT) can improve left ventricular ejection fraction (LVEF), it is not known whether a specific level of improvement will predict future ...implantable cardioverter defibrillator (ICD) therapy.
METHODS AND RESULTS—CRT-defibrillator (CRT-D) was implanted in 423 patients at 1 institution between October 2, 2001 and January 19, 2007. A retrospective analysis was performed to evaluate the relationship between post–CRT-D LVEF and ICD therapy for ventricular tachyarrhythmias. A landmark population of 270 patients, with post–CRT-D LVEF measured and no ICD therapy within 1 year of device implantation, was followed for subsequent outcomes. Of these, 22 patients (8.2%) had subsequent appropriate ICD therapy over a median follow-up of 1.5 years. The estimated 2-year risk of appropriate ICD therapy is 3.0% (95% confidence interval 95% CI, 0%–6.3%), 2.1% (95% CI, 0%–5.0%), and 1.5% (95% CI, 0%–3.9%) for post–CRT-D LVEF of 45%, 50%, and 55%, respectively. In patients with a primary prevention indication for CRT-D, the estimated 2-year risk is 3.3% (95% CI, 0%–7.3%), 2.5% (95% CI, 0%–6.1%), and 1.9% (95% CI, 0%–5.1%) for post–CRT-D LVEF of 45%, 50%, and 55%, respectively.
CONCLUSIONS—When a CRT responder demonstrates near normalization in LVEF to ≥45%, the incidence of ICD therapy for ventricular arrhythmias becomes low. Future studies are needed to determine whether an ICD is still needed in some of these patients at the time of generator replacement.
Recently, the American College of Cardiology Foundation in collaboration with the Heart Rhythm Society published appropriate use criteria (AUC) for implantable cardioverter-defibrillators and cardiac ...resynchronization therapy. These criteria were developed to critically review clinical situations that may warrant implantation of an implantable cardioverter-defibrillator or cardiac resynchronization therapy device, and were based on a synthesis of practice guidelines and practical experience from a diverse group of clinicians. When the AUC was drafted, the writing committee recognized that some of the scenarios that were deemed "appropriate" or "may be appropriate" were discordant with the clinical requirements of many payers, including the Medicare National Coverage Determination (NCD). To charge Medicare for a procedure that is not covered by the NCD may be construed as fraud. Discordance between the guidelines, the AUC, and the NCD places clinicians in the difficult dilemma of trying to do the "right thing" for their patients, while recognizing that the "right thing" may not be covered by the payer or insurer. This commentary addresses these issues. Options for reconciling this disconnect are discussed, and recommendations to help clinicians provide the best care for their patients are offered.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPUK, ZAGLJ, ZRSKP
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