Sacubitril/Valsartan and Cognitive Outcomes in Heart Failure With Reduced Ejection Fraction.

Background: Recent trial data refute concerns about neurocognitive off-target effects of neprilysin inhibition with sacubitril and suggest benefit in patients with heart failure and ejection fraction >40%. We hypothesized that sacubitril/valsartan is associated with improved cognitive outcomes in patients with heart failure and reduced ejection fraction (HFrEF). Objectives: The purpose of this study was to compare 3-year cognitive outcomes in patients with HFrEF who receive sacubitril/valsartan vs angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). Methods: Retrospective cohort study of: 1) 11,313 adults with HFrEF (International Classification of Diseases-10th Revision-Clinical Modification [ICD-10-CM] codes: I50.2 or I50.4) started on sacubitril/valsartan between 1/1/2015 and 12/31/2019; and 2) 11,313 propensity matched patients receiving ACEI/ARB during that time. Data were obtained from the TriNetX Research Network, encompassing 41 health care organizations in the United States. Primary endpoint was the composite of cognitive decline (ICD-10-CM: R41.8), dementia (ICD-10-CM: F01-F03), and Alzheimer's disease (ICD-10-CM: G30). Results: At 3 years, 858 patients on sacubitril/valsartan met the primary endpoint vs 1,209 on ACEI/ARB (3-year incidence: 10.7% vs 15.0%; HR: 0.69; 95% CI: 0.63-0.75; P < 0.001), with consistently lower rates of cognitive decline (9.5% vs 13.3%; HR: 0.69; 95% CI: 0.63-0.76; P < 0.001), dementia (3.4% vs 5.0%; HR: 0.65; 95% CI: 0.57-0.77; P < 0.001), and Alzheimer's disease (0.6% vs 1.3%; HR: 0.48; 95% CI: 0.35-0.66; P < 0.001) in the sacubitril/valsartan cohort. Results were consistent in matched sex and race subgroups. Three-year mortality was 22.0% on sacubitril/valsartan vs 24.6% on ACEI/ARB (HR: 0.89; 95% CI: 0.84-0.94; P < 0.001). Conclusions: Sacubitril/valsartan was associated with lower 3-year rates of neurocognitive disorders when compared to ACEI/ARBs in patients with HFrEF.

QT interval measurement in ventricular pacing: Implications for assessment of drug effects and pro-arrhythmia risk.

QT interval prolongation is a known risk factor for development of malignant ventricular arrhythmias. Measurement of the QT interval is difficult in the setting of ventricular pacing (VP), which can prolong depolarization and increase the QT interval, overestimating repolarization time. VP and cardiac resynchronization therapies have become commonplace in modern cardiac care and may contribute to repolarization heterogeneity and subsequent increased risk for ventricular arrhythmias including Torsades de Pointes. It is imperative for the clinician caring for acutely ill cardiac patients to understand the relationship between QT interval prolongation, both drug-induced and pacing-induced, and repolarization changes with subsequent ventricular arrhythmia risk. In this review, we discuss the components of QT interval assessment for arrhythmogenic risk including arrhythmogenic QT prolongation, methods for adjusting the QT interval to identify repolarization changes, methods to adjust for heart rate, and propose a framework for medication management to assess for drug-induced long QT syndrome in patients with VP.

Electrical Storm in a Case of Bilateral Pheochromocytomas.

BACKGROUND Pheochromocytomas are catecholamine-secreting tumors that develop within the chromaffin cells of the adrenal glands. They most commonly present with hypertension, and the classic triad of symptoms is headaches, palpitations, and diaphoresis. Electrical storm (ES) is defined as at least 3 sustained episodes of ventricular tachycardia (VT), ventricular fibrillation (VF), or appropriate shocks from an implanted cardioverter-defibrillator (ICD) within 24 h. We discuss the case of a 63-year-old man with known bilateral pheochromocytomas who presented with ES prompting multiple ICD shocks, possibly exacerbated by catecholamine surge from his adrenal tumors. CASE REPORT The patient was a 63-year-old man with an extensive medical history including ischemic cardiomyopathy and congestive heart failure with reduced ejection fraction presented with multiple syncopal episodes secondary to persistent monomorphic ventricular tachycardia (MMVT), polymorphic ventricular tachycardia (PMVT), and VF requiring ICD shocks. He had known bilateral pheochromocytomas. ES was attributed to catecholamine excess in the setting of these tumors, so VT ablation was deferred pending tumor removal. Alpha blockade was initiated preoperatively, and the patient subsequently underwent bilateral adrenalectomy; however, he continued to sustain tachyarrhythmias and eventually died despite resuscitative efforts. CONCLUSIONS Bilateral pheochromocytomas are rare adrenal tumors. In even more infrequent situations, they can cause ES secondary to adrenergic stimulation from catecholamine surges. It is worth considering pheochromocytoma in patients with refractory ES, as treating these tumors could potentially reduce the frequency of this dangerous arrhythmia.