Dilated cardiomyopathy review in Circulation

The review is open access full text. I have highlighted some sections below that are of particular interest.

Definitions

From the review:

The term dilated cardiomyopathy (DCM) refers to a spectrum of heterogeneous myocardial disorders that are characterized by ventricular dilation and depressed myocardial performance in the absence of hypertension, valvular, congenital, or ischemic heart disease.5

In clinical practice, the pathogenesis of heart failure (HF) has often been placed into 2 categories: ischemic and nonischemic cardiomyopathy. The term nonischemic cardiomyopathy has been interchangeably used with DCM. Although this approach might be practical, it fails to recognize that nonischemic cardiomyopathy can include cardiomyopathies caused by volume or pressure overload (such as hypertension or valvular heart disease) that are not conventionally accepted under the definition of DCM.1,5

The diagnostic evaluation

Figure 1 is very helpful and should be viewed in the original. A few key points from the figure follow:

Family history is an extremely important part of the initial evaluation given the frequency of familial DCM.

An ischemic work up is indicated if there are ischemic signs, symptoms or risk factors. In some patients over 35 lacking these features it still may be necessary if the etiology remains unknown after evaluation.

Myocardial biopsy for the diagnosis of giant cell/fulminant myocarditis is indicated in any of the following situations: acute decompensation requiring inotropic or mechanical support; type 2 heart block; sustained or symptomatic VT; lack of response of the heart failure syndrome to guideline based medical management within 2 weeks.

Biopsy may be indicated in occasional other situations where certain specific myocardial diseases are considered (see text).

Cardiac MRI may be indicated, particularly for infiltrative diseases.

Disease specific considerations: amyloidosis

The section on amyloidosis is long and loaded with good practical information such that I cannot do justice to it here. I will make these points:

First, I have reviewed cardiac amyloidosis extensively in prior posts. [1] [2] [3] [4] [5] [6] [7] [8]

Also there was this concerning unique aspects of pharmacologic management of heart failure due to cardiac amyloidosis:

Digoxin should be avoided in patients with amyloidosis (Level of Evidence C). Digoxin binds to amyloid fibrils and thus can predispose to toxicity even in the setting of normal serum digoxin levels.56

Calcium channel antagonists (nifedipine or verapamil) should not be administered, because they bind to amyloid fibrils and can result in exaggerated hypotensive and negative inotropic responses (Level of Evidence C).57

Alcoholic cardiomyopathy

In addition to standard guideline based treatment of heart failure there is no disease specific treatment other than alcohol cessation.

Cocaine related cardiomyopathy

Some general considerations, from the review:

Although cocaine abuse has been associated with acute coronary events and regional myocardial injury, long-term cocaine use also has been associated with global DCM without the presence of coronary artery disease (CAD) .. This has been termed cocaine-related cardiomyopathy and implies direct toxicity of cocaine on the myocardium.

Concerning treatment:

Recommendations With Moderate Level of Consensus for Cocaine-Related Cardiomyopathy

It is reasonable to treat patients with cocaine-related cardiomyopathy who have demonstrated abstinence for greater than 6 months with standard therapy for LV dysfunction, including β-blockers (Level of Evidence C).

In patients at risk for relapse for cocaine abuse, nonselective β-blocker treatment with α1-, β1-, or β2-receptor antagonism is reasonable because of potential protection against the unopposed α-agonism effects of cocaine with β1-receptor antagonist treatment alone (Level of Evidence C).

Methamphetamine and related drugs

Cessation of use is the only disease specific recommendation. I have previously reviewed this topic here.

Chemotherapeutic agents

The major culprits are anthracyclines but there are others. Cardiotoxicity may occur at lower doses than previously thought. This may be due to greater sensitivity of detection. A troponin leak acutely after first administration is predictive of clinical cardiac toxicity. Early implementation of guideline based therapies may improve function and prognosis. Much more in the full text.

Peripartum cardiomyopathy

Prognosis is variable. Up to two thirds may recover. A few progress to transplant. Treatment is according to the general heart failure guidelines with the exception of drugs contraindicated in pregnancy and during lactation. Bromocriptine as a disease specific adjunct has yet to be established.

Sarcoidosis

Here are a few points from the article:

Autopsy series suggest that 20% to 50% of patients with sarcoidosis have some degree of cardiac involvement228,232,233; however, only a fraction of these patients have clinically recognized cardiac sarcoidosis…

Diagnostic criteria for cardiac sarcoidosis have been proposed that rely on pathological demonstration of cardiac granulomas or noninvasive evidence of cardiac involvement in a patient with pathologically proven extracardiac sarcoidosis…

In patients with clinically evident cardiac sarcoidosis, complete heart block is a common finding…

Because the myocardial lesions in cardiac sarcoidosis are patchy, and many involve only the LV, an RV EMB provides diagnostic evidence of cardiac sarcoidosis in only 25% to 50% of autopsy-confirmed cases.232 Cardiac MRI with late gadolinium enhancement has emerged as a valuable imaging tool for the diagnosis of cardiac involvement in sarcoidosis…

Corticosteroids are the mainstay of therapy for sarcoidosis.228,229,231 ..Although there are no randomized controlled trials that have established the efficacy of corticosteroids in cardiac sarcoidosis, retrospective studies suggest benefit .. On the basis of observational studies, steroid therapy in patients with established cardiac sarcoidosis and active inflammation should be initiated before LV systolic function declines..Corticosteroids are commonly initiated at a high dose (prednisone 40–60 mg daily) and tapered off slowly over a period of months if clinical and imaging features remain stable or improve…

Patients with cardiac sarcoidosis and reduced LVEF or symptomatic HF should also be treated with standard HF therapy.1 However, because fatal arrhythmias account for 25% to 65% of deaths caused by cardiac sarcoidosis, particular attention is needed to identify patients who would benefit from placement of a permanent pacemaker with an ICD.228,229,231 Although limited, current evidence suggests that ICDs could prevent death caused by dangerous arrhythmias or sudden cardiac death in patients with reduced LVEF, as well as those with relatively preserved LVEF.2,231 In support of this recommendation, the 2012 American College of Cardiology Foundation (ACCF)/AHA/Heart Rhythm Society guidelines for device-based therapy listed cardiac sarcoidosis as a reasonable indication for ICD implantation, with a Class IIa recommendation.240,241

Myocarditis

This section of the paper is very dense and should be read in the original. I will list only a few points here.

The term myocarditis means inflammation of the myocardium. It does not point to a specific etiology. Some specific myocardial diseases such as sarcoidosis covered separately above may be considered forms of myocarditis.

The indications for biopsy are controversial. The paper gives a reasonable approach. There is a set of noninvasive clinical criteria that can be applied if biopsy is considered impractical. These criteria are provided in the text.

Concerning treatment, note this from the paper:

Myocarditis that presents as DCM should be treated per current guidelines for systolic HF.1,3 Individual trials and a meta-analysis suggest that immunosuppression is generally not indicated for the management of acute lymphocytic myocarditis in adults. In cases of giant cell myocarditis, cardiac sarcoidosis, or eosinophilic myocarditis, treatments directed at modifying the immune response should be considered…

Device therapy may be indicated for certain malignant ventricular arrhythmias but not solely for low EF, since ventricular function may improve as inflammation subsides.

HIV can cause DCM

In the heart failure work up, patients with DCM and risk factors for HIV should be tested for HIV as a possible etiology of DCM.

Chagas diseases

Patients who present with DCM and have epidemiologic risk factors should be screened.

Connective tissue and autoimmune diseases

From the paper:

Autoimmune diseases have long been established as rare causes of cardiomyopathy and HF. There are several proposed mechanisms, including immune-mediated myocarditis, progressive fibrosis, and apoptosis with resultant restrictive and dilated phenotypes, progressive atherosclerosis with subsequent ischemic cardiomyopathy, and HF as a result of therapies used for the primary rheumatologic disorder.289 The more well-described associations between autoimmune/rheumatologic disorders and HF include systemic lupus erythematosus (SLE), scleroderma, RA, dermatomyositis, and polyarteritis nodosa (PAN). Sporadic case reports have also associated HF with ankylosing spondylitis, psoriatic arthritis, celiac sprue, vasculitis, and inclusion body myositis through a variety of mechanisms.

Obesity cardiomyopathy

The association of obesity with heart failure is now well enough recognized to warrant this designation. However, according to the article:

Although the concept of a cardiomyopathy related to obesity has been described previously,355–357 severe LV systolic dysfunction occurs uncommonly because of obesity alone, and the presence of LV systolic dysfunction should trigger an investigation for other contributory factors before it is attributed to obesity alone.

Multiple mechanisms were discussed in the paper. Beyond those, obesity can be a cause of the syndrome of high output heart failure. In a recent series, for example, obesity was identified as the etiology of high output heart failure in 31%. Additional factors include obesity's now well known association with atrial fibrillation [9] [10] and the disturbed sodium balance inherent in obesity due to lowered levels of natriuretic peptides.

Thyroid cardiolyopathy

The pathogenesis is incompletely understood. From the article:

Triiodothyronine (T3) generally increases the force and speed of systolic contraction and the speed of diastolic relaxation, through its effects on myosin isoforms and calcium-handling proteins.368–370 In addition, T3 decreases vascular resistance, including coronary vascular tone, and increases coronary arteriolar angiogenesis. Thyroid hormones can also promote both physiological and pathological myocardial hypertrophies.371 Hypothyroidism promotes myocardial fibrosis by stimulating fibroblasts, whereas the reverse is seen in hyperthyroidism..Hyperthyroidism and hypothyroidism can both lead to cardiovascular injury, including HF. However, a DCM related only to the thyroid disorder is present only in a small proportion of these patients.

The hemodynamic effects of hyperthyroidism include decreased systemic vascular resistance, increased resting heart rate and LV contractility, and enhanced isovolumic ventricular relaxation.373 Decreased systemic vascular resistance stimulates renin release with activation of the angiotensin-aldosterone axis,…

Growth hormone disorders

Consider these if the clinical picture fits.

Stress cardiomyopathy, chronic tachycardia myopathy and PVC induced cardiomyopathy

I have discussed these entities extensively in earlier posts to numerous to link here.

LBBB induced cardiomyopathy

It is well known that myocardial diseases capable of producing DCM can cause LBBB. On the other hand, less well known is the fact that LBBB itself, even if initially an isolated finding, can lead to DCM. Device therapy (resynchronization) may be helpful.

Genetic causes

This section deals with, in addition to familial DCM and its several inheritance patterns, left ventricular non-compaction and arrhythmogenic cardiomyopathy, formerly known as arrhythmogenic right ventricular dysplasia. From the paper:

DCM was initially believed to be inherited in a small percentage of cases until Michels et al475 showed that ≈20% of patients had family members with echocardiographic evidence of DCM when family screening was performed. More recently, inherited familial DCM has been shown to occur in 30% to 50% of cases, with autosomal dominant inheritance being the predominant pattern of transmission; X-linked, autosomal recessive, and mitochondrial inheritance patterns are less common but occur.

Duchenne and Becker muscular dystrophy are genetic causes of DCM but were not mentioned.

Iron overload cardiomyopathy

This can be as a result of hereditary hemochromatosis or chronic transfusions or iron infusions. Screening for iron overload is recommended in the evaluation of new cases of DCM although by the time DCM presents due to iron overload it may be too late for disease specific treatment to be beneficial.

Eosinophilic syndromes

Although this category is included in a review of DCM, it presents initially as a restrictive CM. From the paper:

The diagnosis of hypereosinophilic syndrome is made in the presence of eosinophils greater than 1500/μL..Echocardiography and MRI can be helpful in the diagnosis of eosinophilic myocarditis; however, myocardial biopsy remains the gold standard. After diagnosis, evaluation for secondary causes is essential.. If hypereosinophilic syndrome is suspected, a hematology consultation is warranted.. Corticosteroid therapy is generally considered primary therapy for eosinophilic myocarditis, but its efficacy is not well supported.

Low tidal volume ventilation for ARDS: we have been slow on the uptake

From a recent study:

Objective: Low tidal volume ventilation lowers mortality in the acute respiratory distress syndrome. Previous studies reported poor low tidal volume ventilation implementation. We sought to determine the rate, quality, and predictors of low tidal volume ventilation use.

Design: Retrospective cross-sectional study.

Setting: One academic and three community hospitals in the Chicago region.

Patients: A total of 362 adults meeting the Berlin Definition of acute respiratory distress syndrome consecutively admitted between June and December 2013.

Measurements and Main Results: Seventy patients (19.3%) were treated with low tidal volume ventilation (tidal volume less than 6.5 mL/kg predicted body weight) at some time during mechanical ventilation. In total, 22.2% of patients requiring an FIO2 greater than 40% and 37.3% of patients with FIO2 greater than 40% and plateau pressure greater than 30 cm H2O received low tidal volume ventilation. The entire cohort received low tidal volume ventilation 11.4% of the time patients had acute respiratory distress syndrome. Among patients who received low tidal volume ventilation, the mean (SD) percentage of acute respiratory distress syndrome time it was used was 59.1% (38.2%), and 34% waited more than 72 hours prior to low tidal volume ventilation initiation. Women were less likely to receive low tidal volume ventilation, whereas sepsis and FIO2 greater than 40% were associated with increased odds of low tidal volume ventilation use. Four attending physicians (6.2%) initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset for greater than or equal to 50% of their patients, whereas 34 physicians (52.3%) never initiated low tidal volume ventilation within 1 day of acute respiratory distress syndrome onset. In total, 54.4% of patients received a tidal volume less than 8 mL/kg predicted body weight, and the mean tidal volume during the first 72 hours after acute respiratory distress syndrome onset was never less than 8 mL/kg predicted body weight.

Conclusions: More than 12 years after publication of the landmark low tidal volume ventilation study, use remains poor. Interventions that improve adoption of low tidal volume ventilation are needed.

Though I had long sensed something like this I was surprised that the utilization was that low.

Pooled analysis of ODYSSEY trials: LDL reduction (even extreme reduction) matters, even with non-statin treatments

From the paper, published in Circulation:

Background: A continuous relationship between reductions in low-density lipoprotein cholesterol (LDL-C) and major adverse cardiovascular events (MACE) has been observed in statin and ezetimibe outcomes trials down to achieved levels of 54 mg/dL. However, it is uncertain whether this relationship extends to LDL-C levels less than 50 mg/dL. We assessed the relationship between additional LDL-C, non–high-density lipoprotein cholesterol, and apolipoprotein B100 reductions and MACE among patients within the ODYSSEY trials that compared alirocumab with controls (placebo/ezetimibe), mainly as add-on therapy to maximally tolerated statin.

Methods: Data were pooled from 10 double-blind trials (6699 patient-years of follow-up). Randomization was to alirocumab 75/150 mg every 2 weeks or control for 24 to 104 weeks, added to background statin therapy in 8 trials. This analysis included 4974 patients (3182 taking alirocumab, 1174 taking placebo, 618 taking ezetimibe). In a post hoc analysis, the relationship between average on-treatment lipid levels and percent reductions in lipids from baseline were correlated with MACE (coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization) in multivariable analyses.

Results: Overall, 33.1% of the pooled cohort achieved average LDL-C less than 50 mg/dL (44.7%–52.6% allocated to alirocumab, 6.5% allocated to ezetimibe, and 0% allocated to placebo). In total, 104 patients experienced MACE (median time to event, 36 weeks). For every 39 mg/dL lower achieved LDL-C, the risk of MACE appeared to be 24% lower (adjusted hazard ratio, 0.76; 95% confidence interval, 0.63–0.91; P=0.0025). Percent reductions in LDL-C from baseline were inversely correlated with MACE rates (hazard ratio, 0.71; 95% confidence interval, 0.57–0.89 per additional 50% reduction from baseline; P=0.003). Strengths of association materially similar to those described for LDL-C were observed with achieved non–high-density lipoprotein cholesterol and apolipoprotein B100 levels or percentage reductions.

Conclusions: In a post hoc analysis from 10 ODYSSEY trials, greater percentage reductions in LDL-C and lower on-treatment LDL-C were associated with a lower incidence of MACE, including very low levels of LDL-C (less than 50 mg/dL). These findings require further validation in the ongoing prospective ODYSSEY OUTCOMES trial.

Ectopy captured on the 12 lead ECG and future events

From an abstract at AHA 2016:

Methods: We sought to determine if the presence of at least one PAC would predict AF and at least one PVC would predict HF using a single standard (10-second) ECG ...

Results: Among 5,577 CHS participants followed for a median 12 years, a 12-lead ECG PAC (4%) was associated with 60% increased risk of AF (HR 1.6; 95% CI 1.3-2.0; P less than 0.001; Figure) and a PVC (5%) with a 30% increased risk of HF (HR 1.3; 95% CI 1.0-1.6; P = 0.021) and a decline in left ventricular ejection fraction (OR 2.8, 95% CI 1.3-6.1, p=0.008) after multivariable adjustment...

Conclusions: Based on a single standard ECG, the presence of any atrial ectopy predicted AF and any ventricular ectopy predicted HF.

Dexmedetomidine versus haloperidol in delirious non intubated ICU patients

From a recent paper:

Objectives: To evaluate the clinical effectiveness, safety, and cost of dexmedetomidine for the treatment of agitated delirium refractory to haloperidol in nonintubated critically ill patients.

Design: Nonrandomized, controlled trial.

Setting: Intensive care department of a tertiary care nonprofit hospital.

Patients: All consecutive admissions to a medical-surgical ICU with a diagnosis of agitated delirium.

Interventions: Initial haloperidol titration: all patients received IV bolus doses of haloperidol until agitation was controlled (Richmond Agitation Sedation Scale scoring range, 0 to −2) or reaching the maximum daily dose. Group comparison: patient responders to haloperidol (control group) were compared with nonresponders (dexmedetomidine group).

Measurements and Main Results: A total of 132 nonintubated patients were treated with haloperidol in the initial haloperidol titration phase. Forty-six patients (34.8%; 95% CI, 26.0–43.1%) did not respond to haloperidol, and 86 patients (65.2%; 95% CI, 56.3–73.0%) were responders. During the group comparison phase, dexmedetomidine achieved a higher percentage of time in satisfactory sedation levels than did haloperidol (92.7% [95% CI, 84.5–99.8%] vs 59.3% [95% CI, 48.6–69.3%], respectively; p = 0.0001). Haloperidol was associated with 10 cases (11.6% [95% CI, 6.5–21.2%]) of oversedation and two (2.0% [0.4–8%]) of corrected QT lengthening. Direct cost of dexmedetomidine was 17 times greater than haloperidol, but it achieved a mean savings of $4,370 per patient due to the reduction in length of ICU stay.

Conclusions: In the study conditions, dexmedetomidine shows to be useful as a rescue drug for treating agitation due to delirium in nonintubated patients in whom haloperidol has failed, and it seems to have a better effectiveness, safety, and cost-benefit profile than does haloperidol.

End of rotation hand-offs are risky

And the ACGME duty hour regs may have made it worse.

Common ECG findings and the risk of cardiac arrest

From a poster presentation at AHA 2016:

Methods: We cross-linked individuals who had an ECG recording between 2001 and 2011 in primary care with the Danish Cardiac Arrest Register and identified OHCAs of presumed cardiac cause. Multivariable cause-specific Cox regression was used to estimate the association between the ECG abnormalities and OHCA and calculate the absolute 10-year risk of OHCA for men and women with and without known cardiac disease for different age groupings…

Results: A total of 326,227 individuals were included in the study and of those 2,667 suffered an OHCA during a median follow-up of 4 years. The following ECG findings were strongly associated with OHCA: ST-depression without atrial fibrillation (AF), left bundle branch block, and non-specific intraventricular block.

A composite of commonly observed ECG markers may predict sudden cardiac arrest

–-according to an abstract presented at the AHA 2016 sessions.

Early coronary angiography after out of hospital cardiac arrest

---was associated with improved survival to hospital discharge in this systematic review and meta-analysis. (Poster presentation at AHA 2016).

Real world experience with the Medtronic Reveal monitor

From an abstract presented at the AHA 2016 sessions:

Results: A total of 233 patients were included in the study..The indications for implantation were syncope (37.3%), palpitations (24%), AF management (18%), near syncope (5.2%), cryptogenic stroke (3.9%), bradycardia (3.9%), NSVT (1.7%) and long QT (1.3%). A total of 89 (39%) had a diagnosis made during the follow-up time 8 ±4 months..Diagnoses made were AF 22(24.7%), SVT 17(19%), Sick sinus syndrome 10(11%), symptomatic bradycardia 2 (2%), advanced heart block 4 (4.4%), PVC 4 (4.4%), VT 1(1%), other 29 (32.5%). These diagnoses led to change in medication 19 (21%), office visits 17 (19%), radiofrequency ablation 23 (26%), pacemaker implantation 18 (20%), ICD implantation 4 (4%), and miscellaneous 9 (10%). 24 patients underwent device explantation. A total of 3440 CareLink transmissions occurred during the follow up (mean of 15 transmissions per patient).

Chemical defibrillation with IV potassium

From a presentation at AHA 2016:

Introduction: Potassium-based cardioplegia is used in the operating theater to induce asystole. This effect is rapidly reversed with wash-out of the potassium resulting in resumption of electrical activity. This retrospective study examined 5 patients with refractory ventricular fibrillation (VF) cardiac arrest who achieved normal sinus rhythm after chemical defibrillation with exogenous KCl or resolution of endogenous hyperkalemia.

Methods: From December 2015 to May 2016, 19 patients were transported to the University of Minnesota in ongoing refractory VF as part of the Minnesota Resuscitation Consortium Advanced Perfusion and Reperfusion Cardiac Life Support Strategy. ECMO was initiated on arrival. Coronary angiography was performed and significant coronary artery disease was treated as necessary. Three patients had continued VF despite multiple shocks and treatment with amiodarone, lidocaine, metoprolol, and propofol. These patients were given KCl 0.5 mEq/kg bolus as salvage therapy after 90-120 minutes of VF. Defibrillation was administered as needed…

Results: Of the 3 patients that received exogenous potassium bolus, 2 achieved sustained ROSC. The third patient suffered recurrent VF after 30 seconds of sinus rhythm and went on to die. One of the 2 patients that achieved ROSC survived to hospital discharge while 1 patient suffered severe anoxic brain injury and died. The average peak potassium level in these 3 patients was 7.2 mmol/L with normalization within 25 minutes. The EKG showed asystole immediately after treatment with spontaneous return of normal sinus rhythm within 10 minutes.

Bag the banana bag in favor of the optimal metabolic cocktail for critically ill alcoholics

From a recent review:

Objective: Patients with a chronic alcohol use disorder presenting to the ICU may be deficient in important vitamins and electrolytes and are often prescribed a “banana bag” as a reflexive standard of therapy. The difficulty of diagnosing Wernicke’s encephalopathy in the critical care setting is reviewed. Furthermore, whether the contents and doses of micronutrients and electrolytes in standard banana bags meet the needs of critically ill patients with an alcohol use disorder is assessed based on available evidence...

Study Selection and Data Extraction: Articles relevant to Wernicke’s encephalopathy, vitamin and electrolyte deficiencies in patients with alcohol use disorders, and alcoholic ketoacidosis were selected...

Data Synthesis: Of these deficiencies, thiamine is the most important for the practicing clinician to assess and prescribe replacement in a timely manner. Based on a pharmacokinetic assessment of thiamine, the banana bag approach likely fails to optimize delivery of thiamine to the central nervous system. Folic acid and magnesium may also merit supplementation although the available data do not allow for as strong a recommendation...

Conclusions: ..for patients with a chronic alcohol use disorder admitted to the ICU with symptoms that may mimic or mask Wernicke’s encephalopathy, we suggest abandoning the banana bag and utilizing the following formula for routine supplementation during the first day of admission: 200–500 mg IV thiamine every 8 hours, 64 mg/kg magnesium sulfate (approximately 4–5 g for most adult patients), and 400–1,000 μg IV folate. If alcoholic ketoacidosis is suspected, dextrose-containing fluids are recommended over normal saline.

Increasing use of advanced therapies, declining mortality in cardiac arrest

From a poster presentation at AHA 2016:

Methods: The Healthcare Cost and Utilization Project’s Nationwide Inpatient Sample was utilized to identify a cohort of adults hospitalized with CA, identified through International Classification of Diseases-9 codes…

Results: In-hospital all-cause mortality significantly decreased over the 7-year study period (65.5%, 63.4%, 59.3%, 57.9%, and 57.0%, 56.0%, and 56.3% from 2006-2012). From 2006-2012, there was an overall rise in the use of coronary angiogram (12.8%, 13.0%, 14.7%, 15.0%, 14.3%, 14.7%, and 15.8%), percutaneous coronary intervention (PCI) (7.5%, 7.1%, 8.4%, 8.1%, 8.1%, 8.4%, and 8.9%), TH (0.2%, 0.3%, 0.6%, 1.2%, 1.9%, 2.8%, and 3.0%), and ECMO (0.1%, 0.1%, 0.1%, 0.2%, 0.2%, 0.3%, and 0.4%)…

Conclusions: During 2006-2012, a decline in mortality was accompanied by a steady rise in use of advanced therapies, including ECMO, TH, coronary angiogram, and coronary revascularization. Patients of younger age and with CAD were more likely to receive these advanced therapies.

Your syncope admission: could it be PE?

From a recent NEJM report:

Background

The prevalence of pulmonary embolism among patients hospitalized for syncope is not well documented, and current guidelines pay little attention to a diagnostic workup for pulmonary embolism in these patients.

Methods

We performed a systematic workup for pulmonary embolism in patients admitted to 11 hospitals in Italy for a first episode of syncope, regardless of whether there were alternative explanations for the syncope. The diagnosis of pulmonary embolism was ruled out in patients who had a low pretest clinical probability, which was defined according to the Wells score, in combination with a negative d-dimer assay. In all other patients, computed tomographic pulmonary angiography or ventilation–perfusion lung scanning was performed. Results

Results

A total of 560 patients (mean age, 76 years) were included in the study. A diagnosis of pulmonary embolism was ruled out in 330 of the 560 patients (58.9%) on the basis of the combination of a low pretest clinical probability of pulmonary embolism and negative d-dimer assay. Among the remaining 230 patients, pulmonary embolism was identified in 97 (42.2%). In the entire cohort, the prevalence of pulmonary embolism was 17.3% (95% confidence interval, 14.2 to 20.5). Evidence of an embolus in a main pulmonary or lobar artery or evidence of perfusion defects larger than 25% of the total area of both lungs was found in 61 patients. Pulmonary embolism was identified in 45 of the 355 patients (12.7%) who had an alternative explanation for syncope and in 52 of the 205 patients (25.4%) who did not.

Conclusions

Pulmonary embolism was identified in nearly one of every six patients hospitalized for a first episode of syncope

But, as pointed out by the blogger at Emergency Medicine Literature of Note, this should not be as shocking as it sounds (and will be spun by the popular media). As pointed out there:

The primary issue here is the almost certain inappropriate generalization of these results to dissimilar clinical settings. During the study period, there were 2,584 patients presenting to the Emergency Department with a final diagnosis of syncope. Of these, 1,867 were deemed to have an obvious or non-serious alternative cause of syncope and were discharged home. Thus, less than a third of ED visits for syncope were admitted, and the admission cohort is quite old – with a median age for admitted patients of 80 (IQR 72-85). There is incomplete descriptive data given regarding their comorbidities, but the authors state admission criteria included “severe coexisting conditions” and “a high probability of cardiac syncope on the basis of the Evaluation of Guidelines in Syncope Study score.” In short, their admission cohort is almost certainly older and more chronically ill than many practice settings.

Then, there are some befuddling features presented that would serve to inflate their overall prevalence estimate. A full 40.2% of those diagnosed with pulmonary embolism had “Clinical signs of deep-vein thrombosis” in their lower extremities, while 45.4% were tachypneic and 33.0% were tachycardic. These clinical features raise important questions regarding the adequacy of the Emergency Department evaluation; if many of these patients with syncope had symptoms suggestive of PE, why wasn’t the diagnosis made in ED? If even only the patients with clinical signs of DVT were evaluated prior to admission, those imaging studies would have had a yield for PE of 65%, and the prevalence number seen in this study would drop from 17.3% to 10.3%. Further evaluation of either patients with tachypnea or tachycardia might have been similarly high-yield, and further reduced the prevalence of PE in admitted patients.

Put another way, it is likely that many of these patients with PE had all the red flags. It has long been known that PE can present with syncope. When it does it tends (in my subjective experience) to be massive or submassive and would likely yield electrocardiographic or echocardiographic clues. Selective use of imaging based on clinical assessment would likely find these patients. So, I tend to agree with the blogger that while this study should not change practice all that much it in all likelihood will.

Non invasive ventilation for respiratory failure following abdominal surgery

From a recent JAMA paper:

Importance It has not been established whether noninvasive ventilation (NIV) reduces the need for invasive mechanical ventilation in patients who develop hypoxemic acute respiratory failure after abdominal surgery.

Objective To evaluate whether noninvasive ventilation improves outcomes among patients developing hypoxemic acute respiratory failure after abdominal surgery.

Design, Setting, and Participants Multicenter, randomized, parallel-group clinical trial conducted between May 2013 and September 2014 in 20 French intensive care units among 293 patients who had undergone abdominal surgery and developed hypoxemic respiratory failure (partial oxygen pressure less than 60 mm Hg or oxygen saturation [Spo2] less than or equal to 90% when breathing room air or less than 80 mm Hg when breathing 15 L/min of oxygen, plus either [1] a respiratory rate above 30/min or [2] clinical signs suggestive of intense respiratory muscle work and/or labored breathing) if it occurred within 7 days after surgical procedure.

Interventions Patients were randomly assigned to receive standard oxygen therapy (up to 15 L/min to maintain Spo2 of 94% or higher) (n = 145) or NIV delivered via facial mask (inspiratory pressure support level, 5-15 cm H2O; positive end-expiratory pressure, 5-10 cm H2O; fraction of inspired oxygen titrated to maintain Spo2 greater than or equal to 94%) (n = 148).

Main Outcomes and Measures The primary outcome was tracheal reintubation for any cause within 7 days of randomization. Secondary outcomes were gas exchange, invasive ventilation–free days at day 30, health care–associated infections, and 90-day mortality.

Results Among the 293 patients (mean age, 63.4 [SD, 13.8] years; n=224 men) included in the intention-to-treat analysis, reintubation occurred in 49 of 148 (33.1%) in the NIV group and in 66 of 145 (45.5%) in the standard oxygen therapy group within+ 7 days after randomization (absolute difference, −12.4%; 95% CI, −23.5% to −1.3%; P = .03). Noninvasive ventilation was associated with significantly more invasive ventilation–free days compared with standard oxygen therapy (25.4 vs 23.2 days; absolute difference, −2.2 days; 95% CI, −0.1 to 4.6 days; P = .04), while fewer patients developed health care–associated infections (43/137 [31.4%] vs 63/128 [49.2%]; absolute difference, −17.8%; 95% CI, −30.2% to −5.4%; P = .003). At 90 days, 22 of 148 patients (14.9%) in the NIV group and 31 of 144 (21.5%) in the standard oxygen therapy group had died (absolute difference, −6.5%; 95% CI, −16.0% to 3.0%; P = .15). There were no significant differences in gas exchange.

Conclusions and Relevance Among patients with hypoxemic respiratory failure following abdominal surgery, use of NIV compared with standard oxygen therapy reduced the risk of tracheal reintubation within 7 days. These findings support use of NIV in this setting.

Noninvasive ventilation in neuromuscular respiratory failure

Surprisingly, it can be useful in neuromuscular respiratory failure of a variety of causes with the notable exception of GBS. From a recent review:

Recent findings: Myasthenic crisis represents the paradigmatic example of the neuromuscular condition that can be best treated with noninvasive ventilation. Timely use of noninvasive ventilation can substantially reduce the duration of ventilatory assistance in these patients. Noninvasive ventilation can also be very helpful after extubation in patients recovering from an acute cause of neuromuscular respiratory failure who have persistent weakness. Noninvasive ventilation can improve quality of survival in patients with advanced motor neuron disorder (such as amyotrophic lateral sclerosis) and muscular dystrophies, and can avoid intubation when these patients present to the hospital with acute respiratory failure. Attempting noninvasive ventilation is not only typically unsuccessful in patients with Guillain–Barre syndrome, but can also be dangerous in these cases.

Summary: Noninvasive ventilation can be very effective to treat acute respiratory failure caused by myasthenia gravis and to prevent reintubation in other neuromuscular patients, but should be used cautiously for other indications, particularly Guillain–Barre syndrome.

Negative pressure pulmonary edema

Here is a review in Chest. From the review:

Negative-pressure pulmonary edema (NPPE) or postobstructive pulmonary edema is a well-described cause of acute respiratory failure that occurs after intense inspiratory effort against an obstructed airway, usually from upper airway infection, tumor, or laryngospasm. Patients with NPPE generate very negative airway pressures, which augment transvascular fluid filtration and precipitate interstitial and alveolar edema. Pulmonary edema fluid collected from most patients with NPPE has a low protein concentration, suggesting hydrostatic forces as the primary mechanism for the pathogenesis of NPPE. Supportive care should be directed at relieving the upper airway obstruction by endotracheal intubation or cricothyroidotomy, institution of lung-protective positive-pressure ventilation, and diuresis unless the patient is in shock. Resolution of the pulmonary edema is usually rapid, in part because alveolar fluid clearance mechanisms are intact.

Mitral valve prolapse and sudden cardiac death

Here is an interesting case report in the green journal in which a patient presenting in cardiac arrest was found to have mitral valve prolapse (with a flail leaflet) and a markedly prolonged QT. Genetic analysis revealed a novel repolarization prolonging sodium channel mutation as well as a desmoplakin gene mutation of uncertain significance. Of interest, this latter mutation is one of the ones associated with arrhythmogenic right ventricular cardiomyopathy.

During the surge of interest in MVPduring the 1980s there was a belief that it was associated with sudden cardiac death but the mechanism was unclear and the purported association has since been disputed. There has also long been suspected an association between MVP and long QT.

Mean platelet volume as a biomarker for PE

In this study the test characteristics were as good as a D dimer.

More data on the macrovascular benefit of pioglitazone: pioglitazone after stroke or TIA

From a recent NEJM study:

Methods

In this multicenter, double-blind trial, we randomly assigned 3876 patients who had had a recent ischemic stroke or TIA to receive either pioglitazone (target dose, 45 mg daily) or placebo. Eligible patients did not have diabetes but were found to have insulin resistance on the basis of a score of more than 3.0 on the homeostasis model assessment of insulin resistance (HOMA-IR) index. The primary outcome was fatal or nonfatal stroke or myocardial infarction.

Results

By 4.8 years, a primary outcome had occurred in 175 of 1939 patients (9.0%) in the pioglitazone group and in 228 of 1937 (11.8%) in the placebo group (hazard ratio in the pioglitazone group, 0.76; 95% confidence interval [CI], 0.62 to 0.93; P=0.007). Diabetes developed in 73 patients (3.8%) and 149 patients (7.7%), respectively (hazard ratio, 0.48; 95% CI, 0.33 to 0.69; P less than 0.001). There was no significant between-group difference in all-cause mortality (hazard ratio, 0.93; 95% CI, 0.73 to 1.17; P=0.52). Pioglitazone was associated with a greater frequency of weight gain exceeding 4.5 kg than was placebo (52.2% vs. 33.7%, P less than 0.001), edema (35.6% vs. 24.9%, P less than 0.001), and bone fracture requiring surgery or hospitalization (5.1% vs. 3.2%, P=0.003).

Conclusions

In this trial involving patients without diabetes who had insulin resistance along with a recent history of ischemic stroke or TIA, the risk of stroke or myocardial infarction was lower among patients who received pioglitazone than among those who received placebo. Pioglitazone was also associated with a lower risk of diabetes but with higher risks of weight gain, edema, and fracture.

Background on the possible macrovascular benefits of pioglitazone here.

Managing peri-procedural hemorrhage risk

Here is a recent review in Chest.

The abstract lists the procedures considered in the review:

Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy, and lumbar puncture constitute a majority of the procedures performed in patients who are hospitalized.

Of particular interest is the controversy around patients with coagulopathy, either inherent or due to anticoagulants. There is no evidence, and no recommendation from the review, to support avoidance of necessary procedures or prophylactic factor replacement except for LP. In the case LP, though the risk of bleeding is very low an abundance of caution is advised based on expert opinion and rationale. From the review:

Given the paucity of data regarding optimal platelet levels for LP and the potential risks of hematoma, consensus guidelines recommend platelet count of 50,000/mL or greater, with clinical judgment guiding practice when platelet counts are between 20,000 and 49,000/mL…

Based on expert opinion and observational data, the recommendations suggest that therapeutic systemic anticoagulation be held prior to spinal anesthesia or LP.

Special considerations apply to NOACs. From the review:

Direct oral anticoagulants, such as inhibitors of thrombin or factor Xa, are increasingly being used in place of vitamin K antagonists. At this time, recommendations for periprocedural management of these medications are based on expert opinion. These recommendations include holding direct oral anticoagulants for a 24-hour window before and after low-risk procedures and 5 days prior to high-risk procedures.

More evidence favoring lactated ringers over saline

From a recent article:

Objectives: To assess the impact of the percentage of fluid infused as Lactated Ringer (%LR) during the first 2 days of ICU admission in hospital mortality and occurrence of acute kidney injury.

Design: Retrospective cohort.

Setting: Analysis of a large public database (Multiparameter Intelligent Monitoring in Intensive Care-II).

Patients: Adult patients with at least 2 days of ICU stay, admission creatinine lower than 5 mg/dL, and that received at least 500 mL of fluid in the first 48 hours.

Interventions: None.

Measurement and Main Results: 10,249 patients were included in mortality analysis and 8,085 were included in the acute kidney injury analysis. For acute kidney injury analysis, we excluded patients achieving acute kidney injury criteria in the first 2 days of ICU stay. Acute kidney injury was defined as stage 2/3 Kidney Disease: Improving Global Outcomes creatinine criteria and was assessed from days 3–7. The effects of %LR in both outcomes were assessed through logistic regression controlling for confounders. Principal component analysis was applied to assess the effect of volume of each fluid type on mortality. Higher %LR was associated with lower mortality and less acute kidney injury. %LR effect increased with total volume of fluid infused. For patients in the fourth quartile of fluid volume (greater than 7 L), the odds ratio for mortality for %LR equal to 75% versus %LR equal to 25% was 0.50 (95% CI, 0.32–0.79; p less than 0.001). Principal component analysis suggested that volume of Lactated Ringer and 0.9% saline infused had opposite effects in outcome, favoring Lactated Ringer.

Conclusions: Higher %LR was associated with reduced hospital mortality and with less acute kidney injury from days 3–7 after ICU admission. The association between %LR and mortality was influenced by the total volume of fluids infused.

It's pretty impressive to me that in cases of large volume resuscitation the mortality for those in whom 75% of the volume was LR was half that of those in whom 25% was LR.

Fluid balance and mortality in sepsis

From a recent study:

Objectives: Excessive fluid therapy in patients with sepsis may be associated with risks that outweigh any benefit. We investigated the possible influence of early fluid balance on outcome in a large international database of ICU patients with sepsis.

Design: Observational cohort study.

Setting: Seven hundred and thirty ICUs in 84 countries.

Patients: All adult patients admitted between May 8 and May 18, 2012, except admissions for routine postoperative surveillance. For this analysis, we included only the 1,808 patients with an admission diagnosis of sepsis. Patients were stratified according to quartiles of cumulative fluid balance 24 hours and 3 days after ICU admission.

Measurements and Main Results: ICU and hospital mortality rates were 27.6% and 37.3%, respectively. The cumulative fluid balance increased from 1,217 mL (-90 to 2,783 mL) in the first 24 hours after ICU admission to 1,794 mL (-951 to 5,108 mL) on day 3 and decreased thereafter. The cumulative fluid intake was similar in survivors and nonsurvivors, but fluid balance was less positive in survivors because of higher fluid output in these patients. Fluid balances became negative after the third ICU day in survivors but remained positive in nonsurvivors. After adjustment for possible confounders in multivariable analysis, the 24-hour cumulative fluid balance was not associated with an increased hazard of 28-day in-hospital death. However, there was a stepwise increase in the hazard of death with higher quartiles of 3-day cumulative fluid balance in the whole population and after stratification according to the presence of septic shock.

Conclusions: In this large cohort of patients with sepsis, higher cumulative fluid balance at day 3 but not in the first 24 hours after ICU admission was independently associated with an increase in the hazard of death.

Management of coagulopathy in liver diasease

From a recent review:

Conclusions: Dynamic changes to hemostasis occur in patients with hepatic insufficiency. Routine laboratory tests of hemostasis are unable to reflect these changes and should not be used exclusively to evaluate coagulopathy. Newer testing methods are available to provide data on the entire spectrum of clotting but are not validated in acute bleeding. Prohemostatic agents utilized to prevent bleeding should only be considered when the risk of bleeding outweighs the risk of thrombotic complications. Restrictive transfusion strategies may avoid exacerbation of acute bleeding. Prophylaxis against and treatment of thromboembolic events are necessary and should consider patient specific factors.

Factors in delays in antibiotic administration in patients with septic shock

Recently published:

Design: In a retrospective cohort of critically ill patients with septic shock.

Setting: Twenty-four ICUs.

Patients: A total of 6,720 patients with septic shock.

Interventions: None.

Measurements and Main Results: Higher Acute Physiology Score (+24 min per 5 Acute Physiology Score points; p less than 0.0001); older age (+16 min per 10 yr; p less than 0.0001); presence of comorbidities (+35 min; p less than 0.0001); hospital length of stay before hypotension: less than 3 days (+50 min; p less than 0.0001), between 3 and 7 days (+121 min; p less than 0.0001), and longer than 7 days (+130 min; p less than 0.0001); and a diagnosis of pneumonia (+45 min; p less than 0.01) were associated with longer times to antimicrobial therapy. Two variables were associated with shorter times to antimicrobial therapy: community-acquired infections (–53 min; p less than 0.001) and higher temperature (–15 min per 1°C; p less than 0.0001). After adjusting for confounders, admissions to academic hospitals (+52 min; p less than 0.05), and transfers from medical wards (medical vs surgical ward admission; +39 min; p less than 0.05) had longer times to antimicrobial therapy. Admissions from the emergency department (emergency department vs surgical ward admission, –47 min; p less than 0.001) had shorter times to antimicrobial therapy.

Conclusions: We identified clinical and organizational factors that can serve as evidence-based targets for future quality-improvement initiatives on antimicrobial timing. The observation that academic hospitals are more likely to delay antimicrobials should be further explored in future trials.

This is important because in septic shock mortality increases with passage of time until antibiotic administration. These results suggest that increased patient complexity drives delay. Deceptive and indolent presentations appear to be associated with delay as evidenced by the finding of shorter times for higher temperatures. For already hospitalized patients, the longer they had been in the hospital the longer the delay. Might complacency regarding patients near the end of their stay drive this? Particularly intriguing is the fact that academic medical centers had longer delays (+52 minutes). I have to wonder if this relates to more restrictive antibiotic policies and layers of approval embedded at such institutions.

Managing peri-procedural hemorrhage risk

Here is a recent review in Chest.

The abstract lists the procedures considered in the review:

Central venous catheterization, arterial catheterization, paracentesis, thoracentesis, tube thoracostomy, and lumbar puncture constitute a majority of the procedures performed in patients who are hospitalized.

Of particular interest is the controversy around patients with coagulopathy, either inherent or due to anticoagulants. There is no evidence, and no recommendation from the review, to support avoidance of necessary procedures or prophylactic factor replacement except for LP. In the case LP, though the risk of bleeding is very low an abundance of caution is advised based on expert opinion and rationale.

From the review:

Given the paucity of data regarding optimal platelet levels for LP and the potential risks of hematoma, consensus guidelines recommend platelet count of 50,000/mL or greater, with clinical judgment guiding practice when platelet counts are between 20,000 and 49,000/mL…

Based on expert opinion and observational data, the recommendations suggest that therapeutic systemic anticoagulation be held prior to spinal anesthesia or LP.

Special considerations apply to NOACs. From the review:

Direct oral anticoagulants, such as inhibitors of thrombin or factor Xa, are increasingly being used in place of vitamin K antagonists. At this time, recommendations for periprocedural management of these medications are based on expert opinion. These recommendations include holding direct oral anticoagulants for a 24-hour window before and after low-risk procedures and 5 days prior to high-risk procedures.

Left ventricular non compaction

Reviewed in JACC.