Sunday, February 19, 2017

Genetic variants and the efficacy of clopidogrel in stroke and TIA

Background: The association of genetic polymorphisms and clopidogrel efficacy in patients with ischemic stroke or transient ischemic attack (TIA) remains controversial. We performed a systematic review and meta-analysis to assess the association between genetic polymorphisms, especially CYP2C19 genotype, and clopidogrel efficacy for ischemic stroke or TIA.

Methods: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to June 24, 2016. Studies that reported clopidogrel-treated patients with stroke or TIA and with information on genetic polymorphisms were included. The end points were stroke, composite vascular events, and any bleeding.

Results: Among 15 studies of 4762 patients with stroke or TIA treated with clopidogrel, carriers of CYP2C19 loss-of-function alleles (*2, *3, and *8) were at increased risk of stroke in comparison with noncarriers (12.0% versus 5.8%; risk ratio, 1.92, 95% confidence interval, 1.57–2.35; P less than 0.001). Composite vascular events were also more frequent in carriers of CYP2C19 loss-of-function alleles than in noncarriers (13.7% versus 9.4%; risk ratio, 1.51, 95% confidence interval, 1.10–2.06; P=0.01), whereas bleeding rates were similar (2.4% versus 3.1%; risk ratio, 0.89, 95% confidence interval, 0.58–1.35; P=0.59). There was no evidence of statistical heterogeneity among the included studies for stroke, but there was for composite vascular events. Genetic variants other than CYP2C19 were not associated with clinical outcomes, with the exception that significant associations of PON1, P2Y12, and COX-1 with outcomes were observed in 1 study.

Conclusions: Carriers of CYP2C19 loss-of-function alleles are at greater risk of stroke and composite vascular events than noncarriers among patients with ischemic stroke or TIA treated with clopidogrel.

Saturday, February 18, 2017

More evidence for obesity as a risk factor for atrial fibrillation

From a recently published study:


We analyzed data from 2,717 participants of the Health, Aging, and Body Composition Study. Adiposity measures were BMI, abdominal circumference, subcutaneous and visceral fat area, and total and percent fat mass. We determined the associations between the adiposity measures and 10-year incidence of AF using Cox proportional hazards models and assessed for their racial differences in these estimates.


In multivariable-adjusted models, 1-SD increases in BMI, abdominal circumference, and total fat mass were associated with a 13% to 16% increased AF risk (hazard ratio [HR] 1.14, 95% CI 1.02-1.28; HR 1.16, 95% CI 1.04-1.28; and HR 1.13, 95% CI 1.002-1.27). Subcutaneous and visceral fat areas were not significantly associated with incident AF. We did not identify racial differences in the associations between the adiposity measures and AF.


Body mass index, abdominal circumference, and total fat mass are associated with risk of AF for 10 years among white and black older adults. Obesity is one of a limited number of modifiable risk factors for AF; future studies are essential to evaluate how obesity reduction can modify the incidence of AF.

The evidence is mounting that obesity is a risk factor for atrial fibrillation. The extent to which weight loss intervention will impact atrial fibrillation is less clear.

Friday, February 17, 2017

Performance linked to MI survival???

The title to a recent NEJM paper, Life Expectancy after Myocardial Infarction, According to Hospital Performance, (and there was a positive correlation) is deceptive. From the paper:


We analyzed data from the Cooperative Cardiovascular Project, a study of Medicare beneficiaries who were hospitalized for acute myocardial infarction between 1994 and 1996 and who had 17 years of follow-up. We grouped hospitals into five strata that were based on case-mix severity. Within each case-mix stratum, we compared life expectancy among patients admitted to high-performing hospitals with life expectancy among patients admitted to low-performing hospitals. Hospital performance was defined by quintiles of 30-day risk-standardized mortality rates. Cox proportional-hazards models were used to calculate life expectancy.


The study sample included 119,735 patients with acute myocardial infarction who were admitted to 1824 hospitals. Within each case-mix stratum, survival curves of the patients admitted to hospitals in each risk-standardized mortality rate quintile separated within the first 30 days and then remained parallel over 17 years of follow-up. Estimated life expectancy declined as hospital risk-standardized mortality rate quintile increased. On average, patients treated at high-performing hospitals lived between 0.74 and 1.14 years longer, depending on hospital case mix, than patients treated at low-performing hospitals. When 30-day survivors were examined separately, there was no significant difference in unadjusted or adjusted life expectancy across hospital risk-standardized mortality rate quintiles.


In this study, patients admitted to high-performing hospitals after acute myocardial infarction had longer life expectancies than patients treated in low-performing hospitals. This survival benefit occurred in the first 30 days and persisted over the long term.

The time in question for this study, 1994-1996, was quite a bit before what we know today as the performance movement, in the forms of public reporting and pay incentives, was underway. So what is termed performance in this paper has little to do with performance as the phony surrogate for quality as we know it today. What this study really shows is that hospitals with good overall outcomes also have better outcomes in the more narrowly focused category of myocardial infarction.

Thursday, February 16, 2017

PCSK9 inhibitors: what you need to know

This Medscape review is a little dated but still relevant.

Wednesday, February 15, 2017

Outcome comparisons for type 2 diabetes drugs

Importance Numerous glucose-lowering drugs are used to treat type 2 diabetes.

Objective To estimate the relative efficacy and safety associated with glucose-lowering drugs including insulin.

Data Sources Cochrane Library Central Register of Controlled Trials, MEDLINE, and EMBASE databases through March 21, 2016.

Study Selection Randomized clinical trials of 24 weeks’ or longer duration.

Data Extraction and Synthesis Random-effects network meta-analysis.

Main Outcomes and Measures The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight.

Results A total of 301 clinical trials (1 417 367 patient-months) were included; 177 trials (56 598 patients) of drugs given as monotherapy; 109 trials (53 030 patients) of drugs added to metformin (dual therapy); and 29 trials (10 598 patients) of drugs added to metformin and sulfonylurea (triple therapy). There were no significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality. Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels. Sulfonylurea (odds ratio [OR], 3.13 [95% CI, 2.39 to 4.12]; risk difference [RD], 10% [95% CI, 7% to 13%]) and basal insulin (OR, 17.9 [95% CI, 1.97 to 162]; RD, 10% [95% CI, 0.08% to 20%]) were associated with greatest odds of hypoglycemia. When added to metformin, drugs were associated with similar HbA1C levels, while SGLT-2 inhibitors offered the lowest odds of hypoglycemia (OR, 0.12 [95% CI, 0.08 to 0.18]; RD, −22% [−27% to −18%]). When added to metformin and sulfonylurea, GLP-1 receptor agonists were associated with the lowest odds of hypoglycemia (OR, 0.60 [95% CI, 0.39 to 0.94]; RD, −10% [95% CI, −18% to −2%]).

Conclusions and Relevance Among adults with type 2 diabetes, there were no significant differences in the associations between any of 9 available classes of glucose-lowering drugs (alone or in combination) and the risk of cardiovascular or all-cause mortality. Metformin was associated with lower or no significant difference in HbA1C levels compared with any other drug classes. All drugs were estimated to be effective when added to metformin. These findings are consistent with American Diabetes Association recommendations for using metformin monotherapy as initial treatment for patients with type 2 diabetes and selection of additional therapies based on patient-specific considerations.

It is important to note that this analysis did not distinguish between microvascular and macrovascular causes of all cause and cardiovascular mortality.

Tuesday, February 14, 2017

All forms of obesity correlate with atrial fibrillation risk but some are worse than others

From a recent study:

Methods and Results—We conducted a meta-analysis of 63 observational studies including 352 275 individuals, comparing AF risk for 1-SD increases in epicardial fat, waist circumference, waist/hip ratio, and body mass index. A 1-SD higher epicardial fat volume was associated with a 2.6-fold higher odds of AF (odds ratio, 2.61; 95% confidence interval [CI], 1.89–3.60), 2.1-fold higher odds of paroxysmal AF (odds ratio, 2.14; 95% CI, 1.45–3.16) and, 5.4-fold higher odds of persistent AF (odds ratio, 5.43; 95% CI, 3.24–9.12) compared with sinus rhythm. Likewise, a 1-SD higher epicardial fat volume was associated with 2.2-fold higher odds of persistent compared with paroxysmal AF (odds ratio, 2.19; 95% CI, 1.66–2.88). Similar associations existed for postablation, postoperative, and postcardioversion AF. In contrast, associations of abdominal and overall adiposity with AF were less extreme, with relative risks per 1-SD higher values of 1.32 (95% CI, 1.25–1.41) for waist circumference, 1.11 (95% CI, 1.08–1.14) for waist/hip ratio, and 1.22 (95% CI, 1.17–1.27) for body mass index.

Conclusions—Strong and graded associations were observed between increasing epicardial fat and AF. Moreover, the strength of associations of AF with epicardial fat is greater than for measures of abdominal or overall adiposity.

Monday, February 13, 2017

NSAID use and heart failure exacerbation

More evidence of the cardiorenal risks of NSAIDS in this meta-analysis:


The association between exacerbation of heart failure (HF) and use of non-steroidal anti-inflammatory drugs (NSAIDs) has long been recognized but the data on this adverse effect are limited.


To further characterize this possible association, we conducted a systematic review and meta-analysis of observation studies that reported odds ratio, relative risk, hazard ratio or standardized incidence ratio comparing risk of exacerbation of HF in patients with pre-existing HF who took NSAIDs versus non-users. Pooled risk ratios (RR) and 95% confidence intervals for conventional NSAIDs, celecoxib and rofecoxib were calculated using random-effect, generic inverse variance method.


Six studies were identified and included in our data analysis. Use of conventional NSAIDs was associated with a significantly higher risk of development of exacerbation of HF with the pooled RR of 1.39 (95% CI 1.20–1.62). Elevated risk was also observed among celecoxib and rofecoxib users (RR 1.34, 95% CI 0.98–1.85 and RR 2.04, 95% CI 1.68–2.48). The pooled RR of rofecoxib was significantly higher than conventional NSAIDs (p = 0.02).


Use of NSAIDs is associated with an increased risk of HF exacerbation among patients with pre-existing HF. The excess risk was approximately 40% for conventional NSAIDs and celecoxib. The highest risk was observed among rofecoxib users.

Saturday, February 11, 2017

New (direct) oral anticoagulants in VTE

Here is a recent review.

From the conclusion:

Selective thrombin and FXa inhibitors are a new class of anticoagulant drugs, designed to overcome the unmet needs of current therapy. They are orally active, reach full anticoagulant effects shortly after intake, have a relatively short half-life after discontinuation and, in most clinical circumstances, no regular laboratory monitoring or dose adjustment is required. These characteristics render these agents more manageable and appealing for both patients and physicians than heparins or VKAs, but apart these practical advantages of direct oral anticoagulants, what have we learnt from published phase III trials regarding their efficacy and safety in the clinical setting of VTE? A number of recently published systematic reviews and meta-analyses did pool data from randomised trials and performed indirect comparisons. Collectively, they showed that the four direct anticoagulants currently available have at least a similar efficacy for primary prevention and secondary prevention of VTE recurrence and all-cause mortality compared with standard treatments [50–54]. Pertaining to safety, the main issue is whether or not direct anticoagulants are associated with less bleeding complications that the traditional anticoagulants, particularly VKA antagonists. All in all, it was clearly and consistently shown that direct anticoagulants are associated with less intracranial bleeding than traditional agents, whereas the evidence of their superiority pertaining to other sites of bleeding is more uncertain [51].

Note that in the new ACCP guidelines DOACs are given preference over other oral anticoagulants in all non cancer related VTE.

Friday, February 10, 2017

Non invasive ventilation: ward or ICU?

Design: Prospective, observational, pragmatic study.

Setting: Ordinary wards of a teaching hospital.

Patients: Consecutive patients treated with noninvasive ventilation for acute respiratory failure.

Interventions: None.

Measurements and Main Results: Two-hundred and twenty-patients were enrolled. Mortality rates at 30-day, 90-days, and 1-year follow-up were 20%, 26%, and 34%. When excluding patients with “do-not-resuscitate” status, mortality rates were 13%, 19%, and 28%. The multivariate analyses identified solid cancer, pneumonia in hematologic patients, and do-not-resuscitate status as independent predictors of mortality with postoperative acute respiratory failure associated with improved survival. The same predictors were confirmed when excluding do-not-resuscitate patients from the analyses.

Conclusions: Noninvasive ventilation applied in ordinary wards was effective, with long-term outcomes not different from those reported for ICU settings. Solid cancer, pneumonia in hematologic malignancies, and do-not-resuscitate status predicted mortality, whereas patients with postoperative acute respiratory failure had the best survival rate. Additional studies are required to evaluate noninvasive ventilation efficacy in the wards compared with ICU.

Thursday, February 09, 2017

Membrane active non cardiac drugs and the risk of cardiac arrest

From a poster presentation at AHA 2016:

Introduction: Drugs may increase risk of ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac arrest (SCA) in susceptible individuals by blocking cardiac ion channels. This also applies to drugs prescribed for non-cardiac conditions (non-cardiac drugs) if these drugs possess such properties. A well-known example is non-cardiac drugs that block cardiac potassium channels and cardiac repolarization. These drugs may cause excessive QT-interval prolongation and VT/VF in individuals with reduced repolarization reserve (e.g., Long QT syndrome). Similarly, non-cardiac drugs that block cardiac sodium channels and cardiac depolarization increase VT/VF risk in individuals with reduced depolarization reserve (e.g., Brugada syndrome). We hypothesized that non-cardiac depolarization blocking drugs (DB-drugs) are associated with increased VT/VF risk in the general population.

Methods and results: A community based case-control study was performed. Cases were out-of-hospital SCA victims with documented VT/VF included in the ARREST study in June 2005 - December 2009…

We included 1787 SCA cases (mean age 66 years, 77% male) and matched them to 7666 non-SCA controls. Non-cardiac DB-drugs were used by 81 cases (4.5%) and 249 controls (3.2%), and were associated with a 41% increased SCA risk (ORadj: 1.41 [95% CI: 1.10-1.83] P less than 0.05). Use of two or more DB-drugs was associated with a 5.6-fold risk (OR: 5.63 [1.95-16.23] P less than 0.05)…

Conclusion: Current use of non-cardiac DB-drugs is associated with increased risk of SCA, especially when two or more DB-drugs are used simultaneously.

Wednesday, February 08, 2017

Magnesium levels, magnesium supplementation and neurological outcome following cardiac arrest

Introduction: Therapeutic hypothermia (TH) improves neurological outcomes after cardiac arrest by mitigating cerebral reperfusion injury. Plasma magnesium (Mg) inhibits glutamate release, restores blood brain barrier integrity and decreases brain edema. The neuroprotective role of Mg in cardiac arrest patients undergoing TH is not well established. We sought to determine the relationship of plasma Mg and neurologic outcomes in these patients.

Methods: A cohort of 384 consecutive patients who completed TH (33°C) from 2007 to 2016 was retrospectively studied. We evaluated favorable neurologic outcomes as a function of Mg levels before, during, and after TH as well as the relationship between neurologic outcomes and Mg supplementation during TH…

Patients with favorable neurologic outcomes had lower Mg levels at presentation (2.1 mEq/L vs. 2.2 mEq/L, p=0.031). Mg levels on presentation inversely correlated with favorable neurologic outcomes (r=-0.107). A larger percentage of patients who received magnesium supplementation had favorable neurologic outcomes (33% vs. 22%, p=0.033). We also stratified patients based on Mg levels in increments of 0.2 mEq/L to evaluate neurologic outcomes. A non-statistically significant trend towards worse neurologic outcomes was noted in patients with Mg less than 1.6 mEq/L at 24 hours and greater than 2.7 mEq/L at 24 and 48 hours…

Discussion: Lower Mg levels at presentation and magnesium supplementation during TH were associated with favorable outcomes. Intracellular shift and increased renal excretion of Mg have been associated with TH and could worsen hypomagnesemia on presentation after a cardiac arrest. Mg supplementation may potentiate the beneficial effects of TH.

Tuesday, February 07, 2017

Early repolarization pattern in families of victims of sudden arrhythmic death

From a recent study:

Background—The early repolarization (ER) pattern is associated with sudden death and has been shown to be heritable. Its significance when identified in families affected by sudden arrhythmic death syndrome (SADS) remains unclear…

Conclusions—The ER pattern is more common in SADS family members than controls adjusted in particular for relatedness. The increased prevalence is irrespective of ER subtype and the presence of other inherited arrhythmia syndromes. ER may therefore represent an underlying heritable arrhythmia syndrome or risk factor for sudden death in the context of other cardiac pathology.

Sunday, February 05, 2017

Dilated cardiomyopathy review in Circulation

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


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.


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


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.

Saturday, February 04, 2017

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.