Firibastat: A Novel Brain Aminopeptidase Inhibitor - A New Era of Antihypertensive therapy.

Global incidence and prevalence of hypertension continues to increase and remains a significant challenge. The ever-increasing number of cases are due to comorbid conditions such as obesity and diabetes, as well as lifestyle indiscretions such as excessive salt intake. Hypertension, congestive heart failure, and kidney disease are all conditions resulting from abnormal Renin-Angiotensin-Aldosterone activation and adverse remodeling. Firibastat, a novel Brain Aminopeptidase inhibitor, may be able to help achieve blood pressure control in those with resistant hypertension. In this review article, we will discuss the biochemical pathway of firibastat and various trials assessing drug efficacy in animals and humans. This drug has the potential to curb the risk of uncontrolled hypertension and help improve long term cardiovascular morbidity and mortality.

Syncopal Episodes of Arrhythmogenic Right Ventricular Cardiomyopathy in a Patient with Pre-existing Seizure Disorder.

Arrhythmogenic right ventricular cardiomyopathy (ARVC), is a heritable condition that is an important, and under-recognized cause of sudden cardiac death. Microscopically, it is represented by fibrofatty replacement of myocardium involving the right ventricular inflow area, apex, and infundibulum. Common clinical manifestations of ARVC include palpitations, syncope, chest pain, dyspnea, and sudden cardiac death. This is a case of a 25-year-old male with a history of thalassemia, and tonic-clonic seizure status post head trauma with cystic encephalomalacia in left parietal lobe who described recurrent syncope. He was followed by neurology and maintained only on Lamotrigine. Episodes occurred within the span of four weeks and were without prodrome, lasting only a few seconds. On evaluation, blood pressure was 123/69 mmHg. Neurologic exam was grossly normal. Heart was regular rate and rhythm without gallops, murmur, or rub. An EKG showed normal sinus rhythm with an incomplete right bundle branch block and Epsilon waves in leads V1 and V2 without evidence of Brugada syndrome. The patient was admitted and had a 24-hour electroencephalogram that showed no seizure activity. A 2D Echo showed normal left ventricular function and no valvular disease. Eventual cardiac magnetic resonance imaging (MRI) showed small focal outpouchings of the right ventricular free wall. A diagnosis of ARVC was achieved, and the patient underwent electrophysiology (EP) study and successful implantation of a dual-chamber cardioverter defibrillator.

The Disappearing Murmur: Systolic Anterior Motion of the Mitral Valve Leaflet in a Non-hypertrophic Cardiomyopathy Patient.

Systolic anterior motion (SAM) of the mitral valve is a well-known phenomenon associated with left ventricular outflow tract obstruction and hemodynamic compromise. This finding may occur in patients with or without hypertrophic cardiomyopathy. In this report, a patient with no prior medical history presented to the hospital with left-sided chest pain and high-risk echocardiogram (ECG) findings. Left heart catheterization with coronary angiography was negative for coronary artery disease. His initial examination was significant for a systolic murmur due to the underlying SAM, as demonstrated by transthoracic echocardiogram. During his hospitalization, he developed acute heart failure syndrome as a result of dynamic outflow tract obstruction. He was treated with fluid resuscitation with a resolution of his hemodynamic compromise. On a follow-up examination, there was no murmur and SAM was no longer present on echocardiogram. This case demonstrates the importance of recognizing the clinical manifestations of SAM as well as its role in maintaining an appropriate hemodynamic status.

Quality of meta-analyses for randomized trials in the field of hypertension: a systematic review.

OBJECTIVES: Doubling on average every 6 years, hypertension-related meta-analyses are now published twice weekly and are often considered the highest level of evidence for clinical practice. However, some hypertension specialists and guideline authors view meta-analyses with skepticism. This article evaluates the quality of hypertension-related meta-analyses of clinical trials. METHODS: A systematic search was conducted for meta-analyses of clinical trials recently published over 3.3 years. Specific criteria reproducibly assessed 26 features in the four domains of meta-analysis quality, domains justified by fundamental analytics and extensive research: analyzing trial quality, analyzing heterogeneity, analyzing publication bias, and providing transparency. RESULTS: A total of 143 meta-analyses were identified. A total of 44% had 8+ deficient features with no relation to journal impact factor: odds ratio relating 8+ deficient features to the upper third versus lower third of impact factor = 1.3 (95% confidence limit 0.6-2.9). A total of 56% had all four domains deficient. Quality did not improve over time. Thirty articles (21%) reported statistically significant results (P < 0.05) from inappropriate DerSimonian-Laird models, whereas unreported, appropriate, Knapp-Hartung models gave statistical nonsignificance; 88% of these 30 articles reported the incorrect results in their abstracts. A total of 60% of all meta-analyses failed to conduct analyses in subgroups of quality when indicated, 63% failed to report Tau and Tau, 57% omitted testing for publication bias, none conducted a cumulative analysis for publication bias, and 71-77% omitted mentioning in their abstracts problems of trial quality, heterogeneity, and publication bias. CONCLUSION: Although widespread, deficiencies in hypertension-related meta-analyses are readily corrected and do not represent flaws inherent in the meta-analytic method.