Chiefs’ Inquiry Corner

April 22, 2019

Being an outstanding physician and lifelong learner requires stoking the flames of clinical curiosity.  In Chiefs’ Inquiry Corner (CIC) we attempt to succinctly answer actual clinical questions that have been raised on the wards and in the clinics of NYU’s teaching hospitals.  Our answers are not meant to be all encompassing or practice changing but rather to serve as springboards for further exploration.  For those of us with short attention spans, we hope CIC satisfies that craving for a morsel of knowledge in a digestible format.


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It is well established that most patients who have atrial fibrillation benefit from anticoagulation as a means of reducing risk of stroke.  Mechanistically, patients with other chronic atrial tachyarrythmias are assumed to benefit from a similar therapeutic principle – that of reducing clot formation inside a left atrium unable to contract in an organized fashion and with ongoing subclinical endothelial damage and remodeling. Perhaps the most well studied atrial tachyarrhythmia other than atrial fibrillation is atrial flutter, in which there is some evidence (level C) both for increased stroke risk and anticoagulation benefit, leading the AHA/ACC/HRS guidelines to recommend anticoagulation (grade I).  Although focal atrial tachycardia (FAT) and multifocal atrial tachycardia (MAT) are known to predispose to AFib, the guidelines leave out any reference to anticoagulation, likely because there is little good quality data.  One limited but cited study comprised a single center retrospective case control study in which patients with Holter monitors admitted with ischemic stroke or syncope were assessed for underlying episodes of atrial tachycardia. This study found that there was no difference in the prevalence of AT or the number of beats of AT between groups, casting into some doubt the benefit of systemic anticoagulation in this population. However much research is still needed to better elucidate this claim.

References: Anticoagulation for Atrial Tachycardia

References: ACC/AHA Guidelines  
The HACEK acronym refers to a group of organisms that were grouped together due to their oropharyngeal predominance, low virulence, and preponderance to cause infective endocarditis (IE). They are Haemophilus spp., Aggregatibacter spp., Cardiobacterium hominis, Eikenella corrodens, and Kingella kingae. HACEK organisms are responsible for around 1% of IE, which tends to present more insidiously than gram positive endocarditis. Patients with HACEK-IE have a lower risk of acute heart failure, but are at an increased risk of stroke, vascular, and immunological sequelae of IE. Generally the risk of mortality with HACEK-IE is lower than with non-HACEK IE, with the exception of Haemophilus spp., which carries a mortality rate of up to 35%. Classically, these organisms have been thought to be difficult to culture, but with new techniques of bacterial culture, sensitivities for HACEK organisms have reached 99% within the first 5 days. Positive blood cultures for any bacteria of the HACEK group are highly suggestive of IE if no other focus of infection is identified.

References: HACEK Endocarditis  
Treating hypertension in patients with hypertrophic cardiomyopathy (HC) presents unique challenges due to the altered cardiac physiology in these patients. While vasodilators such angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and dihydropyridine calcium channel blockers (CCBs) are commonly used as first line medications in the general population, these medications are avoided in patients with HC as they can exacerbate outflow tract obstruction and cause hypotension or heart failure symptoms. Due to the limited data available regarding safe treatment options for patients with HC and hypertension, a retrospective cohort study was performed at St. Luke’s-Roosevelt Hospital Center in 2013 to evaluate blood pressure, medication use, and symptoms when using a step-wise, symptom-oriented approach to managing patients with co-existing HC and hypertension. One hundred fifteen patients were included in the study with a mean follow-up of 36 months. The hypertension treatment strategy diverged based on whether the patients were obstructed or non-obstructed – treatment for obstructed patients consisted of optimizing beta blockade, and/or non dihydropyridine CCBs and if symptomatic addition of disopyramide. With this treatment strategy, at follow up fewer obstructed patients were treated with ACE inhibitors or ARBs (42% vs 14%, p< 0.01) and dihydropyridine CCBs (13% vs 4%, p = 0.03). More patients were treated with beta-blockers (62% vs 86%, p less than 0.01), disopyramide therapy (9% vs. 35%, p less than 0.01), and clonidine (3% vs 11%, p=0.02). Average systolic blood pressure decreased from 137 to 131 mmHg (p = 0.01) and the prevalence of uncontrolled hypertension decreased from 56% to 37% (p = 0.01). Although there are notable limitations of this study including its observational nature, single-point measurements of blood pressure, and single-center experience, it provides some guidance regarding safe and effective management of hypertension in patients with HC.

References: HCM Hypertension Management  
Cardiogenic ascites – ascites fluid that accumulates as a direct result of cardiac pathology – is well-described, though comprises only a small percentage of patients with ascites. Prior studies have shown that cardiac ascites can be distinguished from other etiologies of ascites – specifically ascites due to hepatic cirrhosis with portal hypertension – by the ascites fluid protein (AFP) level, with a cut-off AFP greater than 2.5g/dL suggesting a diagnosis of cardiac ascites. Cardiac ascites is an all-encompassing term for ascites that occurs due to cardiac disease, and does not distinguish between ascites fluid that develops acutely as a result of impaired right heart function resulting in portal hypertension and increased sinusoidal dilation versus ascites that develops in a more indolent fashion as a result of increased hepatic congestion leading to fibrosis and ultimately cirrhosis over a period of time. A recent retrospective cohort study questioned whether the use of AFP could be expanded to not simply diagnose cardiac ascites, but to distinguish between etiologies of cardiac ascites. This study compared patients with cardiac ascites with radiographic evidence of cirrhosis to those with non-cirrhotic cardiac ascites, and found that while the serum-ascites albumin gradient (SAAG) was similar between the two cohorts, the average ascites fluid protein was significantly lower in patients with cardiac cirrhosis compared to those with cardiac ascites who were non-cirrhotic (3.66 g/dl vs. 4.31 g/dl p<0.01). Moreover, an AFP less than 4.3g/dl predicted cirrhosis with a sensitivity approaching 95%.  This study suggests that AFP may be used not only to distinguish cardiac from non-cardiac ascites, but to further characterize cardiac ascites into cirrhotic vs. non-cirrhotic phenotypes.

References: AFP in cardiac ascites  
Roflumilast is an oral phosphodiesterase-4 (PDE-4) inhibitor, thought to play a role in decreasing inflammation and causing smooth muscle relaxation in the airways.  In patients with severe, refractory COPD despite maximal therapy, it has been shown to decrease the rate of severe exacerbations.  In a study from the Lancet in 2015, 1,945 patients with severe COPD already on combination long acting beta-2 agonist (LABA) and inhaled corticosteroid (ICS) were randomized to roflumilast at a dose of 500μg daily vs. placebo for one year.   In patients receiving roflumilast, there was a 13.2% relative decrease in the rate of moderate-severe COPD exacerbations and a 24.3% relative decrease in the rate of hospitalizations.  There was no significant decrease in patient’s quality of life. Patients on roflumilast did have higher rates of adverse events compared with placebo (67% vs. 59%), though serious adverse events were similar.  There was no difference in mortality between the groups.  These data are promising and suggest an added beneficial effect of roflumilast on top of standard therapy to prevent exacerbations and hospitalizations for patients with severe COPD.

References: Roflumilast and Severe COPD