Cardiocerebral syndrome

This refers to cognitive dysfunction occurring in heart failure. It has been referred to in various ways through the years. I first blogged about it 11 years ago when it was called cardiac encephalopathy. It has since gained increasing recognition. Here are a few key points from a review and accompanying audio summary in JACC:

There are not only cognitive changes but also structural changes in the brain.

It can occur in both heart failure with reduced EF and heart failure with preserved EF.

It may be at least partially reversible with improvement in cardiac status.

Cerebral autoregulation may be impaired in heart failure.

Neurohumoral activation is contributory.

TNF and other cytokines are elevated and may contribute to cognitive dysfunction.

One third of hospitalized patients with heart failure have been reported to have thiamine deficiency! This may cause brain changes other than the classic Wernicke and Korsakoff syndromes.

Depression is common in heart failure.

What should the clinician do?

Diagnose it via the MMSE or some other clinical tool and exclusion of other causes.

Manage electrolyte problems.

Optimize heart failure management.

Identify and treat depression.

Give thiamine???

Wireless LV endocardial pacing takes CRT to the next level

The SELECT-LV Study, reporting results of the WiSE-CRT system (EBR Systems, Sunnyvale, California) was recently published in JACC. It was a small study, composed of 35 patients who, for one reason or another, had failed conventional CRT.

From the paper:

Background A total of 30% to 40% of patients with congestive heart failure eligible for cardiac resynchronization therapy (CRT) either do not respond to conventional CRT or remain untreated due to an inability or impediment to coronary sinus (CS) lead implantation. The WiSE-CRT system (EBR Systems, Sunnyvale, California) was developed to address this at-risk patient population by performing biventricular pacing via a wireless left ventricular (LV) endocardial pacing electrode.

Objectives The SELECT-LV (Safety and Performance of Electrodes implanted in the Left Ventricle) study is a prospective multicenter non-randomized trial assessing the safety and performance of the WiSE-CRT system.

Methods A total of 35 patients indicated for CRT who had “failed” conventional CRT underwent implantation of an LV endocardial pacing electrode and a subcutaneous pulse generator. System performance, clinical efficacy, and safety events were assessed out to 6 months post-implant.

Results The procedure was successful in 97.1% (n = 34) of attempted implants. The most common indications for endocardial LV pacing were difficult CS anatomy (n =12), failure to respond to conventional CRT (n = 10), and a high CS pacing threshold or phrenic nerve capture (n = 5). The primary performance endpoint, biventricular pacing on the 12-lead electrocardiogram at 1 month, was achieved in 33 of 34 patients. A total of 28 patients (84.8%) had improvement in the clinical composite score at 6 months, and 21 (66%) demonstrated a positive echocardiographic CRT response (greater than or equal to 5% absolute increase in LV ejection fraction). There were no pericardial effusions, but serious procedure/device-related events occurred in 3 patients (8.6%) within 24 h, and 8 patients (22.9%) between 24 h and 1 month.

Conclusions The SELECT-LV study demonstrates the clinical feasibility for the WiSE-CRT system, and provided clinical benefits to a majority of patients within an otherwise “failed” CRT population.

The complications included embolization of the LV electrode, stroke, device related infection and one death from VF during the procedure.

Yes Virginia, LDL really does matter

Numerous authors over the last several years, citing the pleiotropic effects of statins, have refused to believe that LDL reduction is important. This is despite several lines of evidence, as I have pointed out in numerous previous posts [1] [2] [3].

Now comes this systematic review and meta-analysis from JAMA. From the article:

Conclusions and Relevance In this meta-regression analysis, the use of statin and nonstatin therapies that act via upregulation of LDL receptor expression to reduce LDL-C were associated with similar RRs of major vascular events per change in LDL-C. Lower achieved LDL-C levels were associated with lower rates of major coronary events.

Multiple means of LDL reduction appear to reduce events to a similar degree.

“Early” invasive versus selectively invasive strategy for non ST segment ACS

Here is the paper in question. I put the word early in quotes because it meant cath within 48 hours, not an immediate cath. From the paper:

Methods The ICTUS trial was a multicenter, randomized controlled clinical trial that included 1,200 patients with NSTE-ACS and an elevated cardiac troponin T. Enrollment was from July 2001 to August 2003. We collected 10-year follow-up of death, myocardial infarction (MI), and revascularization through the Dutch population registry, patient phone calls, general practitioners, and hospital records. The primary outcome was the 10-year composite of death or spontaneous MI. Additional outcomes included the composite of death or MI, death, MI (spontaneous and procedure-related), and revascularization…

Conclusions In patients with NSTE-ACS and elevated cardiac troponin T levels, an early invasive strategy has no benefit over a selective invasive strategy in reducing the 10-year composite outcome of death or spontaneous MI, and a selective invasive strategy may be a viable option in selected patients.

Don’t confuse this with another debate now raging concerning NSTEMI, which is whether such patients should go to the cath lab immediately rather than wait up to 48 hours. Clearly there are some, quite a few in fact, at least among NSTEMI patients as they are defined according to prevailing performance measures, who should. These patients often have ECG findings which, though not meeting the criteria for STEMI, suggest acute epicardial coronary occlusion or impending occlusion. A closely related debate is whether the STEMI/NSTEMI designation is even useful at all.

NEJM review of Cushing’s syndrome

Some key points from the review follow:

Prior to the obesity epidemic assessment of the pretest probability of Cushing’s syndrome based on physical examination was relatively easy.  Nowadays it is much more difficult to clinically assess patients for Cushing's syndrome merely on the basis of the anabolic manifestations (abdominal obesity and the metabolic syndrome) due to the considerable overlap between Cushing's and the metabolic syndrome with respect to these characteristics.  However, taking into account the antianabolic effects of chronic hypercortisolism (osteoporosis, multiple bruises, thin skin) greatly enhances clinical assessment and if all three of the latter are present the pretest probability is quite high.

The optimal laboratory strategy to confirm the diagnosis is controversial.  The review author recommends a 24 hour urine free cortisol determination for laboratory confirmation followed by an ACTH level for differentiation of the type of Cushing's syndrome.  He decries the use of dexamethasone suppression testing but this view is in dispute.  Other sources (Up to Date and Harrison's) mention dexamethasone suppression testing as having a potential role in the evaluation.  Midnight sampling of plasma or salivary cortisol are also mentioned by the other sources.

Recommendations for inferior petrosal sinus sampling are variable, with the NEJM review calling for a more definitive role for such sampling.  By this point in the evaluation the hospitalist or primary physician would need some help from an endocrinologist.

Periprocedural management of anticoagulation in non-valvular a fib: what the hospitalist needs to know

This expert consensus decision pathway is available as free full text here. It is in line with published guidelines and other posts I have written on this topic. This applies only to non-valvular a fib as the anticoagulation indication.

Carcinoids and other neuroendocrine tumors

This review in the Archives of Pathology and Laboratory Medicine helps clarify the sometimes confusing terminology around the diverse array of these tumors.

Giant cell myocarditis review

Here is a free full text review.

A few points of interest form the paper:

Historically, GCM and cardiac sarcoidosis were often conflated, as both presented in similarly aged patients and could result in a myocarditis characterized by giant cells and granulomas. However, it has since been established that the two are distinct clinicopathologic entities with significant differences in presentation, histologic features, and prognosis…

The disease course is rapid, with a median time of 3 weeks from symptom onset to hospital presentation.6 While GCM appears to have no sex predilection, approximately 20% of cases occur in patients with an autoimmune disorder such as inflammatory bowel disease, celiac disease, thyroiditis, or rheumatoid arthritis—among others.4,10,11 Some cases of GCM are associated with tumors, most often thymoma and lymphoma…

Without appropriate immunosuppressive therapy, the median survival from GCM symptom onset to death or transplant is only 3 months.6 With appropriate immunosuppressive therapy, the 5-year survival rate free of transplant ranges from 52% to 72%.11,15 While the optimal immunosuppressive regimen remains to be defined, a combined double- or triple-drug cyclosporine-based therapy reportedly leads to a partial clinical remission in two-thirds of patients….

The Coombs test: some things you need to know

A nice free full text review in the Archives of Pathology and Laboratory Medicine.

Review of carcinoid heart disease

The full text of this review is available only by subscription, but the audio summary is open access.

Here are a few key points:

Carcinoid tumors (CT) tend to grow slowly and remain asymptomatic for long periods. Carcinoid syndrome (CS), the clinical state resulting from release of mediators by the tumor, generally does not occur until it metastasizes to the liver, though there are exceptions to this rule. CS consists of vasomotor disturbances, flushing, bronchospasm and diarrhea and is primarily mediated by serotonin although other mediators including kinins, histamine and prostaglandins are involved.

Carcinoid heart disease (CHD) is a valvulopathy (most frequently the tricuspid, followed in order of frequency by the pulmonic and then the left sided valves) caused by an inflammatory and fibroproliferative response of valvular endocardium to the circulating mediators, most notably serotonin. Regurgitation is the primary lesion affecting the valves although stenosis can occur to a lesser degree.

It is estimated that 50% of patients with CS go on to develop CHD though that number may be decreasing with improvements in recognition and treatment of CS. Once CHD develops it tends to progress rapidly and worsens the prognosis of patients with CS.

Transcatheter embolization and surgical debulking of liver metastases are indicated in some patients but become less viable options if hepatic congestion has developed due to the risk of acute liver failure and bleeding.

Valve replacement may improve the outlook for selected patients.

Chronic calcium blocker use and reduced mortality in sepsis

From a recent paper:

Abstract

Objectives: Experimental studies suggest that calcium channel blockers can improve sepsis outcome. The aim of this study was to determine the association between prior use of calcium channel blockers and the outcome of patients admitted to the ICU with sepsis.

Design: A prospective observational study.

Setting: The ICUs of two tertiary care hospitals in the Netherlands.

Patients: In total, 1,060 consecutive patients admitted with sepsis were analyzed, 18.6% of whom used calcium channel blockers.

Interventions: None.

Measurements and Main Results: Considering large baseline differences between calcium channel blocker users and nonusers, a propensity score matched cohort was constructed to account for differential likelihoods of receiving calcium channel blockers. Fifteen plasma biomarkers providing insight in key host responses implicated in sepsis pathogenesis were measured during the first 4 days after admission. Severity of illness over the first 24 hours, sites of infection and causative pathogens were similar in both groups. Prior use of calcium channel blockers was associated with improved 30-day survival in the propensity-matched cohort (20.2% vs 32.9% in non-calcium channel blockers users; p = 0.009) and in multivariate analysis (odds ratio, 0.48; 95% CI, 0.31–0.74; p = 0.0007). Prior calcium channel blocker use was not associated with changes in the plasma levels of host biomarkers indicative of activation of the cytokine network, the vascular endothelium and the coagulation system, with the exception of antithrombin levels, which were less decreased in calcium channel blocker users.

In the discussion section the authors mention a possible mechanism:

Here, we show a significantly reduced mortality in ICU patients who were on chronic CCB treatment before development of sepsis. The association between prior CCB use and reduced sepsis mortality was consistent in sensitivity and subgroup analyses. The mechanism by which chronic CCB use may influence sepsis outcome was not revealed by sequential measurements of host response biomarkers reflecting activation of the cytokine network, the vascular endothelium or the coagulation system, and rather may involve partial prevention of cellular toxicity related to sustained elevations in intracellular Ca2+ levels.

Update on the clinical and pathologic aspects of ANCA diseases

Free full text review.

Video laryngoscopy for for endotracheal intubation: better visualization but not better outcomes

Recent study here.

Vancomycin in combination with zosyn increased the risk of AKI

---according to this systematic review and meta-analysis. The authors concluded:

Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.

Type of atrial fibrillation and stroke risk

From a recent paper:

Background—Whether the pattern of atrial fibrillation (AF) modifies the risk/benefit of anticoagulation is controversial…

Conclusions—In ENGAGE AF-TIMI 48 trial, patients with paroxysmal AF suffered fewer thromboembolic events and deaths compared with those with persistent and permanent AF.

Hypotension due to IV acetaminophen

From a recent paper published in Critical Care Medicine:

Objectives: We sought to assess the incidence of acetaminophen-induced hypotension. Our secondary objectives were to describe systemic hemodynamic changes and factors associated with this complication.

Design: Prospective observational study.

Setting: Three ICUs.

Patients: Adult patients requiring IV acetaminophen infusion. Arterial pressure was monitored via an arterial catheter for 3 hours. Hypotension was defined as a decrease in the mean arterial pressure of greater than or equal to 15% compared with the baseline…

Conclusions: Half of the patients who received IV injections of acetaminophen developed hypotension, and up to one third of the observed episodes necessitated therapeutic intervention. Adequately powered randomized studies are needed to confirm our findings, provide an accurate estimation of the consequences of acetaminophen-induced hypotension, and assess the pathophysiologic mechanisms involved.

Treatment decisions for patients with a first seizure

Here is a guideline synopsis published in JAMA. From the article:

Major recommendations Whether to initiate immediate antiepileptic drug (AED) treatment after a first seizure should be based on individualized assessments that weigh the risk of recurrence against the adverse effects of AED therapy, a consideration of the preferences of an educated patient, and the advice that immediate treatment will not improve the long-term prognosis for seizure remission but will reduce the risk of seizures over the subsequent 2 years…

The new guideline emphasizes that clinicians should weigh the individualized risk of seizure recurrence against the adverse effects of AEDs and consider the preferences of patients. For instance, the risk of seizure recurrence in a patient with normal electroencephalogram and brain magnetic resonance imaging results is relatively low at approximately 25% over the next 2 years.8 While some patients may accept the 25% risk, others may consider it too high. Regardless, patients should be advised that immediate treatment may not improve the long-term prognosis for seizure remission but will reduce seizure risk over the next 2 years. Despite avoiding explicit “to treat or not to treat” recommendations, most of the guideline recommendations conform to current clinical practices. States vary widely in driver licensing requirements for patients with epilepsy (https://www.epilepsy.com/driving-laws), as do requirements for physicians to notify state authorities, complicating the provision of accurate instructions to patients.

Therapeutic hypothermia after in hospital cardiac arrest

There have been no RCTs looking at induced hypothermia following in hospital arrest. The 2010 ACLS guidelines recommended hypothermia for out of hospital VF/PVT arrest but only recommended that it be considered for other types of arrest. However the 2015 guidelines extended the recommendation to all post arrest comatose patients regardless of the arrest location. A new cohort study published in JAMA, drawing from a very large database, calls this into question. From the paper:

Importance Therapeutic hypothermia is used for patients following both out-of-hospital and in-hospital cardiac arrest. However, randomized trials on its efficacy for the in-hospital setting do not exist, and comparative effectiveness data are limited.

Objective To evaluate the association between therapeutic hypothermia and survival after in-hospital cardiac arrest.

Design, Setting, and Patients In this cohort study, within the national Get With the Guidelines–Resuscitation registry, 26 183 patients successfully resuscitated from an in-hospital cardiac arrest between March 1, 2002, and December 31, 2014, and either treated or not treated with hypothermia at 355 US hospitals were identified. Follow-up ended February 4, 2015.

Exposure Induction of therapeutic hypothermia.

Main Outcomes and Measures The primary outcome was survival to hospital discharge. The secondary outcome was favorable neurological survival, defined as a Cerebral Performance Category score of 1 or 2 (ie, without severe neurological disability). Comparisons were performed using a matched propensity score analysis and examined for all cardiac arrests and separately for nonshockable (asystole and pulseless electrical activity) and shockable (ventricular fibrillation and pulseless ventricular tachycardia) cardiac arrests.

Results Overall, 1568 of 26 183 patients with in-hospital cardiac arrest (6.0%) were treated with therapeutic hypothermia; 1524 of these patients (mean [SD] age, 61.6 [16.2] years; 58.5% male) were matched by propensity score to 3714 non–hypothermia-treated patients (mean [SD] age, 62.2 [17.5] years; 57.1% male). After adjustment, therapeutic hypothermia was associated with lower in-hospital survival (27.4% vs 29.2%; relative risk [RR], 0.88 [95% CI, 0.80 to 0.97]; risk difference, −3.6% [95% CI, −6.3% to −0.9%]; P = .01), and this association was similar (interaction P = .74) for nonshockable cardiac arrest rhythms (22.2% vs 24.5%; RR, 0.87 [95% CI, 0.76 to 0.99]; risk difference, −3.2% [95% CI, −6.2% to −0.3%]) and shockable cardiac arrest rhythms (41.3% vs 44.1%; RR, 0.90 [95% CI, 0.77 to 1.05]; risk difference, −4.6% [95% CI, −10.9% to 1.7%]). Therapeutic hypothermia was also associated with lower rates of favorable neurological survival for the overall cohort (hypothermia-treated group, 17.0% [246 of 1443 patients]; non–hypothermia-treated group, 20.5% [725 of 3529 patients]; RR, 0.79 [95% CI, 0.69 to 0.90]; risk difference, −4.4% [95% CI, −6.8% to −2.0%]; P less than  .001) and for both rhythm types (interaction P = .88).

Conclusions and Relevance Among patients with in-hospital cardiac arrest, use of therapeutic hypothermia compared with usual care was associated with a lower likelihood of survival to hospital discharge and a lower likelihood of favorable neurological survival. These observational findings warrant a randomized clinical trial to assess efficacy of therapeutic hypothermia for in-hospital cardiac arrest.

The ACLS guidelines now have a dynamic (continuously updating) web page but this study has yet to be mentioned there.

The patient safety movement: how are we doing?

According to the authors of a recent viewpoint article in JAMA, although the decade following the Institute of Medicine Report was widely regarded as a failure, progress may have been made from 2000 to 2014. The data are a little soft, though and it is difficult to tell whether the purported improvement is due to systems improvements, secular trends or pervasive chart doctoring which is believed to have increased over the past few years with the recent external pressures.

The EMPIRICUS trial

From a recent issue of JAMA:

Question Does empirical antifungal therapy increase invasive fungal infection–free survival at day 28 in nonneutropenic critically ill patients with sepsis, multiple Candida colonization, and multiple organ failure exposed to broad-spectrum antibacterials?

Findings In this randomized clinical trial of 260 adults, there was no significant difference in the rate of survivors without any fungal infection at day 28 between micafungin-treated (87/128 [68%]) and placebo-treated (74/123 [60.2%]) groups.

Meaning The use of micafungin as a routine empirical treatment in critically ill patients with suspected fungal infection did not improve fungal infection–free survival at 28 days.

These were patients with hospital acquired suspected infections with multiple risk factors for invasive candida infection (apart from neutropenia and certain other forms of severe immunosuppression). The practice of using antifungals in such patients is widespread. This may be practice changing, though some caveats were pointed out in a related editorial:

The study was well powered to assess difference in mortality between groups and the results are largely generalizable to critically ill patients with characteristics similar to the study inclusion criteria. Nonsignificant improvement in survival was noted among patients with high Sequential Organ Failure Assessment scores, which may suggest that certain critically ill subgroups may benefit from empirical therapy. Additionally, there was low participation among patients with postoperative gastrointestinal leakage and acute necrotizing pancreatitis, among which there is a high risk of invasive fungal infection. Previous studies have shown surgical patients may benefit from empirical therapy.

Based on the above, the “empirical” use of antifungal therapy in such patients may need to be more targeted. (The quotation marks point out that the use of antifungal agents such as is described herein is based more on theory and rationale than evidence and so is hardly empirical).