Topic update: contrast induced AKI

Here is a freefull text review in the journal Cardiorenal Medicine.

Of note:

Volume expansion with saline or bicarb based fluid is recommended for prevention of AKI in high risk patients. Evidence suggests bicarb is superior but the review comes short of recommending one fluid over another.

Evidence is cited in favor of volume expansion and forced diuresis, but the review makes no firm recommendations pending further trials.

Given the mixed results with N-acetylcysteine its use is now considered controversial and no recommendation was given.

Evidence favoring a protective effect of ascorbic acid was cited but no recommendation made.

Evidence favoring a protective effect of statins was cited but no recommendation made.

Conspicuously absent from the review was mention of remote ischemic preconditioning which has shown great promise in recent studies.

Chest compression interruptions and post resuscitation survival

We learned over a decade ago from the Arizona investigators that compression continuity was the most important metric for survival. A new study in Circulation, using a different analytical approach, confirmed the association:

Methods and Results—In 319 patients with ventricular tachycardia/fibrillation out-of-hospital cardiac arrest, we analyzed recordings from all defibrillators used during resuscitation and measured durations of all CPR pauses. Median (25th, 75th percentile) durations in seconds were 32 (22, 52) for the longest pause for any reason, 23 (14, 34) for the longest peri-shock pause, and 24 (11, 38) for the longest non-shock pause. Multivariable regression models showed lower odds for survival per five second increase of the longest overall pause (OR 0.89, 95%CI 0.83-0.95), longest peri-shock pause (OR 0.85, 95%CI 0.77-0.93), and longest non-shock pause (OR 0.83, 95%CI 0.75-0.91). In 36% of cases, the longest pause was a non-shock pause; this subgroup had lower survival than cases where the longest pause was a peri-shock pause (27% vs 44% respectively, p less than 0.01) despite a higher chest compression fraction. Pre-shock pauses were 8 seconds (4, 17) for shock that terminated ventricular fibrillation and 7 seconds (4, 13) for shocks that did not (p=0.18).

One year follow up on the CHANCE trial

From the paper:

Background—The Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events (CHANCE) trial showed that the combined treatment of clopidogrel and aspirin decreases the 90-day risk of stroke without increasing hemorrhage in comparison with aspirin alone, but provided insufficient data to establish whether the benefit persisted over a longer period of time beyond the trial termination. We report the 1-year follow-up outcomes of this trial.

Methods and Results—The trial was a randomized, double-blind, placebo-controlled trial conducted at 114 centers in China. We randomly assigned 5170 patients within 24 hours after onset of minor stroke or high-risk transient ischemic attack to clopidogrel-aspirin therapy (loading dose of 300 mg of clopidogrel on day 1, followed by 75 mg of clopidogrel per day for 90 days, plus 75 mg of aspirin per day for the first 21 days) or to the aspirin-alone group (75 mg/d for 90 days). The primary outcome was stroke event (ischemic or hemorrhagic) during 1-year follow-up. Differences in outcomes between groups were assessed by using the Cox proportional hazards model. Stroke occurred in 275 (10.6%) patients in the clopidogrel-aspirin group, in comparison with 362 (14.0%) patients in the aspirin group (hazard ratio, 0.78; 95% confidence interval, 0.65–0.93; P=0.006). Moderate or severe hemorrhage occurred in 7 (0.3%) patients in the clopidogrel-aspirin group and in 9 (0.4%) patients in the aspirin group (P=0.44).

Conclusions—The early benefit of clopidogrel-aspirin treatment in reducing the risk of subsequent stroke persisted for the duration of 1-year of follow-up.

Benefits of statin use after ishcemic stroke

From the PROSPER study:

From 2007-2011, 77,468 patients who were not taking statins at the time of admission were hospitalized with ischemic stroke; of these, 71% were discharged on statin therapy. After adjustment, statin therapy at discharge was associated with a lower hazard (hazard ratio; 95% confidence interval) of MACE (0.91; 0.87, 0.94), 28 more home-time days following discharge (p less than 0.001), and lower all-cause mortality and readmission. Statin therapy at discharge was not associated with increased risk of hemorrhagic stroke (0.94; 0.72, 1.23). Among statin-treated patients, 31% received a high-intensity dose; after risk adjustment, these patients had similar outcomes compared with moderate-intensity recipients.

Conclusions—In older ischemic stroke patients who were not taking statins at the time of admission, discharge statin therapy was associated with lower risk of MACE and nearly a month more home-time during the 2-year period post-hospitalization.

Carotid endarterectomy versus stenting

From a recent review:

Nonetheless, given the current state of evidence, CEA is generally superior for symptomatic patients with significant ICA stenosis, including those greater than or equal to 70 years of age. CAS is a reasonable alternative in patients with high operative risk, including those with a hostile neck or significant comorbidities such as uncompensated cardiac or pulmonary disease.

Additionally, the American College of Cardiology/American Heart Association guidelines recommend CAS as an alternative to CEA for symptomatic patients at average or low risk of complications associated with CAS if the anticipated rate of periprocedural stroke or mortality is less than 6%.21 This recommendation is based largely on findings from CREST. However, given a lack of consistent evidence for noninferiority of CAS in other RCTs for symptomatic patients, this recommendation remains debatable, and is not reflected in other guidelines.

In asymptomatic patients, the general recommendation is to consider CEA for significant ICA stenosis in patients who have a life expectancy of at least 3 to 5 years, and low risk of perioperative stroke/death (less than 3%). The role of CAS in asymptomatic patients remains to be established. However, given the results from CREST, some guidelines suggest that CAS may be considered as an alternative to CEA in highly selected asymptomatic patients treated at high-volume centers by experienced operators with low stroke/death rates (less than 3%).

More data on the cardiometabolic benefits of exercise

From a recent paper in the Journal of the American Heart Association:

Methods and Results Two researchers selected 160 randomized controlled trials (7487 participants) based on literature searches of Medline, Embase, and Cochrane Central (January 1965 to March 2014). Data were extracted using a standardized protocol. A random‐effects meta‐analysis and systematic review was conducted to evaluate the effects of exercise interventions on cardiorespiratory fitness and circulating biomarkers. Exercise significantly raised absolute and relative cardiorespiratory fitness. Lipid profiles were improved in exercise groups, with lower levels of triglycerides and higher levels of high‐density lipoprotein cholesterol and apolipoprotein A1. Lower levels of fasting insulin, homeostatic model assessment–insulin resistance, and glycosylated hemoglobin A1c were found in exercise groups. Compared with controls, exercise groups had higher levels of interleukin‐18 and lower levels of leptin, fibrinogen, and angiotensin II.

The management of cardiogenic shock

This is a free full text review the need for which is outlined in the opening of the paper:

Contrary to septic shock, there are no international recommendations regarding the management of cardiogenic shock (CS) in intensive care. Reasons include the rarity of the disease, but also the fact that patients with CS often solely receive care in cardiology. Recent European Society of Cardiology (ESC) guidelines on the management of acute heart failure include a section on CS [1]. However, these guidelines are vague for the intensivist and at times obsolete (with regard to vasopressors, for example). The lack of a specific approach to the management of severe forms of CS in the latest international guidelines led our group to draw the following recommendations.

There is a wealth of information here which should be read in the original. I will highlight only a few points of particular interest below.

Cardiogenic shock definition

Cardiogenic shock (CS) is defined as a state of critical end-organ hypoperfusion due to reduced cardiac output. Notably, CS forms a spectrum ranging from mild hypoperfusion to profound shock…

Area 1: epidemiology

In cardiogenic shock, a coronary cause should routinely be sought (strong agreement).

In over 70 % of cases, CS is related to acute myocardial infarction (MI) with ST-segment elevation, with or without mechanical complications (rupture of the septum, of the ventricular wall or of chordae tendineae). However, shock rarely occurs during MI (4.2 to 8.6 % of cases, depending on the study) and is declining…

Area 2: cardiogenic shock in acute myocardial infarction

Predictors of progression to cardiogenic shock, in particular a heart rate >75 beats/min and signs of heart failure, should be sought in all patients with myocardial infarction (strong agreement)….

2-

Coronary angiography, followed by coronary revascularization using angioplasty or exceptionally coronary artery-bypass surgery, is required in cardiogenic shock secondary to acute myocardial infarction irrespective of the time interval since the onset of pain (strong agreement)…

Plasma lactate should be assayed repeatedly (in the absence of epinephrine therapy) to assess the persistence or correction of shock during treatment (strong agreement).

Here the exception of epinephrine use for lactate monitoring is based on the fact that epinephrine causes lactic acidosis by non ischemic mechanisms (type B lactic acidosis) and thus would confound the interpretation of lactate levels.

The recommendations for hemodynamic monitoring and invasive access are based more on expertise. In the case of CVP monitoring they run counter to the latest evidence applied to septic shock:

4-

A central venous catheter placed in the superior vena cava should be used for intermittent (blood sample) or continuous (fiber optic) measurement of central venous oxygen saturation (ScvO2) (strong agreement).

Inasmuch as central venous catheterization is mandatory in shock, particularly in cardiogenic shock, use of this catheter is recommended for intermittent (blood sample) or continuous (fiber optic) measurement of central venous oxygen saturation (ScvO2), which indicates whether cardiac output is appropriate to the metabolic conditions and provides useful information for adaptation of treatment.

5-

Central venous pressure should not be measured because of the constraints of measurement and its limits as a marker of preload and of preload dependency (weak agreement).

6-

In shock refractory to empirical treatment, cardiac output as well as mixed venous oxygen saturation (SvO2) or ScvO2 should be continuously monitored (strong agreement).

7-

We suggest pulmonary artery catheterization in patients with refractory cardiogenic shock and right ventricular dysfunction (weak agreement).

8-

We suggest the use of a transpulmonary thermodilution monitor/pulse wave analysis plus measurement (continuous or intermittent) of mixed venous oxygen saturation (SvO2) or ScvO2 when cardiogenic shock is refractory to initial treatment, in the absence of mechanical assistance and of predominant right ventricular dysfunction (weak agreement)…

Concerning the use of vasoactive agents, the authors recommend norepinephrine for raising perfusion pressure and dobutamine for inotropic support, to raise cardiac output. Although epinephrine could be used to achieve both objectives with one drug the authors prefer the combination of dubutamine and norepinephrine. Dopamine is not recommended.

This recommendation implies that norepinephrine could be infused without a central line:

In prehospital and emergency care, the vasopressor of choice is norepinephrine (weak agreement).

The authors did not elaborate and whether they had in mind interaosseous or peripheral access is not clear.

2-

In proven post-cardiac arrest cardiogenic shock, especially in shockable rhythms, routine coronary angiography is recommended (strong agreement)…

3-

The existence or onset of post-cardiac arrest cardiogenic shock is not a contraindication to therapeutic hypothermia (strong agreement)…

2-

If temporary circulatory support is needed, the use of peripheral extracorporeal membrane oxygenation is preferred (strong agreement)…

In cardiogenic shock, ventricular resynchronization is possible in cases of left-bundle branch block with wide QRS complex (weak agreement).

ESC recommendations do not mention CS as an indication for resynchronization. Resynchronization has enabled improvement of clinical condition and weaning from inotropic agents in patients with severe acute heart failure (NYHA class III-IV). In 15 CS patients with left-bundle branch block, a German team showed that temporary resynchronization of the left ventricle using a lead placed in the coronary sinus (while maintaining atrioventricular synchronous contraction using a right atrial lead) optimized macrocirculatory parameters and reduced blood-lactate concentration [31]. However, because of the absence of literature data of high level of proof, its routine use in CS patients cannot be recommended, because of the risk of infectious and mechanical complications associated with pacemaker implantation.

Here's a recommendation that's bound to be controversial:

In ischemic cardiogenic shock, the hemoglobin level should be maintained at around 10 g/dL

During the very acute phase of cardiogenic shock in which oxygen delivery is low and cardiac output is insufficient to meet metabolic demand, it may be useful to increase hemoglobin levels. Nevertheless, as soon as cardiogenic shock is resolved, the transfusion trigger should to 7 g/dL.

8-

When cardiogenic shock is not ischemic in origin, the hemoglobin level should be maintained above 8 g/dL (weak agreement).

For cardiogenic shock caused by drug overdoses early use of ECMO is advised. In addition:

Adjuvant treatments such as glucagon (beta-blockers), insulin therapy (calcium inhibitors), and lipid emulsion (lipid-soluble cardiotoxic local anesthetic) should be initially used in association with vasopressor/inotrope agents (strong agreement). Medical supportive treatment should not delay use of ECMO in case of refractory shock (weak agreement).

6-

The administration of molar sodium bicarbonate (doses fractionated from 100 to 250 mL up to a maximum total dose of 750 mL) is indicated in toxic shock with intraventricular conduction abnormalities (wide QRS complex), together with other treatments (strong agreement).

during the acute phase (weak agreement).

It goes on to say:

During the very acute phase of cardiogenic shock in which oxygen delivery is low and cardiac output is insufficient to meet metabolic demand, it may be useful to increase hemoglobin levels. Nevertheless, as soon as cardiogenic shock is resolved, the transfusion trigger should to 7 g/dL.

8-

When cardiogenic shock is not ischemic in origin, the hemoglobin level should be maintained above 8 g/dL (weak agreement).

For cardiogenic shock caused by drug overdoses early use of ECMO is advised. In addition:

Adjuvant treatments such as glucagon (beta-blockers), insulin therapy (calcium inhibitors), and lipid emulsion (lipid-soluble cardiotoxic local anesthetic) should be initially used in association with vasopressor/inotrope agents (strong agreement). Medical supportive treatment should not delay use of ECMO in case of refractory shock (weak agreement).

6-

The administration of molar sodium bicarbonate (doses fractionated from 100 to 250 mL up to a maximum total dose of 750 mL) is indicated in toxic shock with intraventricular conduction abnormalities (wide QRS complex), together with other treatments (strong agreement).

For end stage heart disease progressing to CS:

Area 12: cardiogenic shock complicating end-stage heart disease

Patients with severe chronic heart disease should be assessed for their heart transplant eligibility in a center equipped for this intervention (strong agreement).

A patient with end-stage decompensated heart failure considered eligible for heart transplantation should be rapidly managed in the expert center that conducted the assessment (strong agreement).

ECMO/extracorporeal life support is indicated as first-line treatment in the case of progressive or refractory shock (persistent lactic acidosis, low cardiac output, high doses of catecholamines, kidney and/or liver failure) and of cardiac arrest without “no flow” in patients with advanced chronic heart disease with no contraindication for heart transplantation (strong agreement).

In progressive or refractory cardiogenic shock in a patient hospitalized for decompensated heart failure in a center without circulatory support, prompt use of a circulatory support mobile unit to implement veno-arterial ECMO followed by transfer of the patient on ECMO to an expert center is recommended (strong agreement).

Miscellaneous etiologies:

Area 14: other etiologies

Patients with acute heart failure or cardiogenic shock associated with myocarditis should be transferred to an expert center, on ECMO if necessary (strong agreement).

Bromocriptine treatment should be considered in cardiogenic shock complicating peripartum cardiomyopathy after discounting pre-existing or genetic heart disease (weak agreement).

For stress cardiomyopathy the authors recommend minimizing or, if possible, discontinuation of inotropic agents.

Benefits of long term beta blocker use after CABG

From a recent study:

Methods and Results—The study included 5926 consecutive patients who underwent CABG and were discharged alive. The prevalence and consistency of β-blocker use were determined in patients with and without a history of myocardial infarction (MI). β-Blockers were always used in 1280 patients (50.9%) with and 1642 patients (48.1%) without previous MI after CABG. Compared with always users (n=2922, 49.3%), the risk of all-cause death was significantly higher among inconsistent β-blocker users (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.50–2.57), and never using β-blockers was associated with increased risk of both all-cause death (HR, 1.42; 95% CI, 1.01–2.00) and the composite of adverse cardiovascular events (HR, 1.29; 95% CI, 1.10–1.50). In the cohort without MI, the HR for all-cause death was 1.70 (95% CI, 1.17–2.48) in inconsistent users and 1.23 (95% CI, 0.76–1.99) in never users. In the MI cohort, mortality was higher for inconsistent users (HR, 2.14; 95% CI, 1.43–3.20) and for never users (HR, 1.59; 95% CI, 1.07–2.63). Consistent results were obtained in equivalent sensitivity analyses.

Conclusions—In patients with or without previous MI undergoing CABG, the consistent use of β-blockers was associated with a lower risk of long-term mortality and adverse cardiovascular events. Strategies should be developed to understand and improve discharge prescription of β-blockers and long-term patient adherence.

Atorvastatin, simvastatin and sepsis outcomes

Prior research indicates better sepsis outcomes for patients taking statins. According to this new study it matters which statin the patient is taking.

Cotrimoxazole usage in critical illness

This situation does not come up very often. Two examples would be Pneumocystis jovenii and Stenotrophomonas maltophilia. There is a scarcity of data to guide clinicians in dosing the drug in critically ill patients. This review (free full text) presents a summary of what information we do have, and provides dosing recommendations.

Autoimmune long QT syndrome

It appears to be associated with anti-Ro:

Background—Emerging clinical evidence demonstrates high prevalence of QTc prolongation and complex ventricular arrhythmias in patients with anti-Ro antibody (anti-Ro Ab)–positive autoimmune diseases. We tested the hypothesis that anti-Ro Abs target the HERG (human ether-a-go-go–related gene) K+ channel, which conducts the rapidly activating delayed K+ current, IKr, thereby causing delayed repolarization seen as QT interval prolongation on the ECG.

Methods and Results—Anti-Ro Ab–positive sera, purified IgG, and affinity-purified anti-52kDa Ro Abs from patients with autoimmune diseases and QTc prolongation were tested on IKr using HEK293 cells expressing HERG channel and native cardiac myocytes. Electrophysiological and biochemical data demonstrate that anti-Ro Abs inhibit IKr to prolong action potential duration by directly binding to the HERG channel protein. The 52-kDa Ro antigen–immunized guinea pigs showed QTc prolongation on ECG after developing high titers of anti-Ro Abs, which inhibited native IKr and cross-reacted with guinea pig ERG channel.

Conclusions—The data establish that anti-Ro Abs from patients with autoimmune diseases inhibit IKr by cross-reacting with the HERG channel likely at the pore region where homology between anti–52-kDa Ro antigen and HERG channel is present. The animal model of autoimmune-associated QTc prolongation is the first to provide strong evidence for a pathogenic role of anti-Ro Abs in the development of QTc prolongation. It is proposed that adult patients with anti-Ro Abs may benefit from routine ECG screening and that those with QTc prolongation should receive counseling about drugs that may increase the risk for life-threatening arrhythmias.

By way of background here is information on autoimmune disease of the conduction system.

Statins improve outcomes in patients with heart failure and preserved ejection

An anti-inflammatory mechanism is postulated.

What is the prognosis for patients with an asymptomatic type 1 Brugada pattern?

From a recentstudy:

Methods and Results—Patients presenting with spontaneous or drug-induced Brugada type I electrocardiogram (ECG) and no symptoms at our institution were considered eligible. A total of 363 consecutive patients (200 males, 55.1%; mean age: 40.9±17.2 years, 41 (11.3%) with spontaneous type I ECG) were included. Electrophysiological study (EPS) was performed in 321 (88.4%) and ventricular arrhythmias (VA) were induced in 32 (10%). An implantable cardioverter defibrillator (ICD) was implanted in 61 (16.8%). After a mean follow-up time of 73.2±58.9 months, 9 arrhythmic events occurred, accounting for an annual incidence rate of 0.5%. Event free survival was 99.0% at 1 year and 96.2% at 5 years, 95.4% at 10 and 15 years. Univariate analysis identified as risk factors EPS inducibility (HR 11.4, p less than 0.01), spontaneous type I (HR 4.0, p=0.04) and previous sinus node dysfunction (SND) (HR 8.0, 95% CI 1.0 - 63.9, p=0.05). At the multivariate analysis only inducibility remained significant (HR 9.1, p less than 0.01)

Conclusions—Arrhythmic events in asymptomatic BS patients are not insignificant. VA inducibility, spontaneous type I ECG and presence of SND might be considered as risk factors and used to drive long term management.

Stroke management in sickle cell disease

A review from Blood's How I Treat series.

How can asthma deaths be reduced?

Findings from The2014 UK National Review of Asthma Deaths:

The 2014 UK National Review of Asthma Deaths identified potentially preventable factors in two-thirds of the medical records of cases scrutinised

45% of people who died from asthma did not call for or receive medical assistance in their final fatal attack

Overall asthma management, acute and chronic, in primary and secondary care was judged to be good in less than one-fifth of those who died

There was a failure by doctors and nurses to identify and act on risk factors for asthma attacks and asthma death

The rationale for diagnosing asthma was not evident in a considerable number of cases, and there were inaccuracies related to the completion of medical certificates of the cause of death in over half of the cases considered for the UK National Review of Asthma Deaths

Severe AKI post CABG

---was associated with increased long term risk for progressive CKD in this study.

PICCO hemodynamic monitoring

No better than CVP monitoring for patients with sepsis or ARDS in this trial.

Ezetimibe added to statin therapy: LDL matters

From the IMPROVE-IT investigators:

Conclusions

When added to statin therapy, ezetimibe resulted in incremental lowering of LDL cholesterol levels and improved cardiovascular outcomes. Moreover, lowering LDL cholesterol to levels below previous targets provided additional benefit.

The trial involved patients who had had acute coronary syndrome.

With recognition of the powerful pleiotropic effects of statins and the promulgation of the new statin guidelines we have all but forgotten the importance of LDL reduction itself. This was known decades ago based on non statin trials. Nevertheless some have recently made the unwarranted claim that LDL reduction doesn't matter.

How soon should you resume anticoagulation (for atrial fibrillation) after a head bleed?

That question was addressed in a study recently published, drawn from a large database of three registries.  The abstract is worded in a way that is very hard to make sense of and you have to dive into the body of the paper to get real answers.  It turns out that patients who had anticoagulation restarted (at a median time of around a month) did better in terms of not only ischemic events but a composite outcome which included recurrent ICH.  The rate of ICH itself was not significantly different between those who did and those who did not have anticoagulation resumed.

Updated AHA/ADA scientific statement on prevention of cardiovascular disease in type 2 diabetes

This document is available as free full text and a link to the citation is here.

Here are a few noteworthy points:

DM can be defined as an A1C of 6.5 or above, FBS of 126 or above OR two hour PC of 200 or above.

Prediabetes, a risk for not only DM itself but cardiovascular disease, can be defined as A1C of 5.7-6.4, FBS 100-125 OR a two hour PC of 140-199.

An A1C target of less than or equal to 7 is recommended for most patients. This recommendation is controversial. An emerging opinion in the controversy is that while 7 may be a reasonable target, levels below that may have risks that exceed benefits. Microvascular benefit may increase along a continuum of lower and lower A1C levels, even if below 7. Levels pushed below 7 by pharmacologic means, however, (at least using insulin or sulfonylureas) appear to be associated with macrovascular harm. A target of 8 is suggested for certain individuals such as older patients, those prone to hypoglycemia, and those with advanced complications.

According to the document, pharmacologic agents or bariatric surgery warrant consideration for obese patients if desired weight cannot be achieved by lifestyle changes. Weight loss drugs are controversial because any benefits appear to be counterbalanced by adverse outcomes for all agents adequately studied. The article has an extensive discussion of the data concerning bariatric surgery.

Hypoglycemia is now recognized as a driver of cardiovascular disease. The article discusses possible mechanisms which include sympathetic nervous system activation, increase in the QT interval, endothelial dysfunction, platelet activation, coagulation factor activation and activation of inflammatory mediators.