NSTEMI algorithm, metabolic acidemia, and more

Summaries from ACP Hospitalist Weekly.

Rapid rule-out algorithm for NSTEMI deemed safe, effective

The European Society of Cardiology (ESC)'s algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction (NSTEMI) using high-sensitivity cardiac troponin appears safe and effective in triaging patients, a large multicenter study found.

Researchers prospectively enrolled patients in six countries who presented to the ED with symptoms of NSTEMI from May 2006 to April 2016. High-sensitivity cardiac troponin T (hs-cTnT) and high-sensitivity cardiac troponin I (hs-cTnI) were measured at presentation and after one hour. The ESC hs-cTn 0/1-h algorithm uses assay-specific cutoff levels for hs-cTnT and hs-cTnI, in conjunction with other clinical information such as clinical assessment and electrocardiography, to triage patients very early to rule out or rule in myocardial infarction. In the current study, negative predictive value (NPV) for NSTEMI was used to quantify rule-out safety, positive predictive value (PPV) was used to quantify rule-in accuracy, and the proportion of patients triaged within one hour was used to quantify overall efficacy. Results were published Aug. 7, 2018, issue of the Journal of the American College of Cardiology.

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Image by Getty Images

NSTEMI prevalence was 17%. Among 4,368 patients for whom hs-cTnT measurements were available, safety of rule-out (NPV, 99.8%; 2,488 of 2,493 patients), accuracy of rule-in (PPV, 74.5%; 572 of 768 patients), and overall efficacy were high, with three-fourths of patients assigned either to rule-out (57%; 2,493 of 4,368 patients) or rule-in (18%; 768 of 4,368 patients). Among 3,500 patients for whom hs-cTnI measurements were available, safety of rule-out (NPV, 99.7%; 1,528 of 1,533 patients), accuracy of rule-in (PPV, 62.3%; 498 of 800 patients), and overall efficacy were high, with more than two-thirds of patients assigned either to rule-out (44%; 1,533 of 3,500 patients) or rule-in (23%; 800 of 3,500 patients). The researchers noted that excellent safety was confirmed in multiple subgroup analyses including patients who presented three hours or less after chest pain onset.

All diagnostic algorithms based on high-sensitivity cardiac troponin should always be used in conjunction with all other information available to the clinicians, including vital signs, 12-lead electrocardiogram, and chest pain characteristics, the authors wrote.

“The combination of the ESC 0/1-h algorithm with quantified clinical judgment seems particular[ly] valuable, as it has been shown to help identify patients with UA [unstable angina], the more benign acute coronary syndrome phenotype. Moreover, it is important to mention that beyond the ESC 0/1-h algorithm, other early biomarker-based strategies also have been developed and seem to justify clinical use,” the authors wrote.

An editorial noted that many patients, particularly low-risk individuals who present at least three hours after the onset of symptoms, can have acute myocardial infarction excluded with high-sensitivity troponin testing, assuming the FDA approves the values used in Europe and in this study.

“Even then, however, caution is advised when dealing with patient subsets such as the elderly, the critically ill, individuals with end-stage renal disease, those who present with atypical symptoms, and perhaps also those who present very early after the onset of symptoms,” the editorial cautioned. “It is likely for these reasons and others that an independent evaluation employing this approach in an emergency medicine setting performed far less well than in the present study.”

Sodium bicarbonate did not improve survival in ICU patients with metabolic acidemia

Receiving sodium bicarbonate did not affect overall survival in ICU patients with severe metabolic acidemia, but it did appear to improve outcomes in the subgroup of patients with acute kidney injury, a recent study found.

The trial included adults with severe metabolic acidemia (pH ≤7.20 and sodium bicarbonate concentration ≤20 mmol/L, plus Paco2 ≤45 mm Hg) and either a Sequential Organ Failure Assessment score of 4 or more or an arterial lactate concentration of 2 mmol/L or more within 48 hours of admission to an ICU. Between May 5, 2017, and May 7, 2017, 389 patients were enrolled in 26 ICUs in France, and they received either 4.2% IV sodium bicarbonate infusion to maintain arterial pH above 7.30 or no sodium bicarbonate. The protocol recommended infusions of 125 to 250 mL in 30 minutes, with a maximum of 1,000 mL within 24 hours. Results were published by The Lancet on June 14, 2018, and appeared in the July 7, 2018, issue.

The study's primary outcome was a composite of death from any cause by day 28 and the presence of at least one organ failure at day 7. It occurred in 71% of the control group compared to 66% of the bicarbonate group (absolute difference estimate, −5.5%; 95% CI, −15.2 to 4.2; P=0.24). Using the Kaplan-Meier method to estimate probability of survival, the researchers found no significant difference overall (46% in controls vs. 55% in bicarbonate patients; P=0.09), but sodium bicarbonate was associated with significantly better survival in a prespecified subgroup of patients with Acute Kidney Injury Network (AKIN) scores of 2 or 3 (63% vs. 46%; P=0.0283). Metabolic alkalosis, hypernatremia, and hypocalcemia were more common in the bicarbonate group, but no life-threatening complications were reported.

The study authors noted that sodium bicarbonate was also associated with less renal replacement therapy, and they speculated that the reduced mortality among patients with acute kidney injury might have resulted from having more days free of vasopressor and renal replacement therapy than controls. This and other studies support the importance of sodium bicarbonate timing, the authors said, noting that almost none of the patients were given sodium bicarbonate after the first 24 hours and that “sodium bicarbonate infusion might have bought time” to avoid or delay renal replacement therapy. Limitations included that no specific control solution was recommended, and future research should look at whether different formulas for sodium bicarbonate infusion affect outcomes.

An accompanying comment said that the lack of survival benefit in the overall population was consistent with previous research but that the results in patients with acute kidney injury are intriguing and require further study.

Infective endocarditis risk increased after many types of medical procedures

A recent study found evidence of an association between several medical procedures and the development of infective endocarditis.

The study included all adult patients treated for endocarditis at hospitals in Sweden between Jan. 1, 1998, and Dec. 31, 2011, for a total of 7,013 cases of infective endocarditis. Using a case-crossover design, the authors compared invasive medical procedures in the 12 weeks before patients developed endocarditis with a corresponding 12-week period in the same patients exactly one year earlier. Results were published by the Journal of the American College of Cardiology on June 11, 2018.

A significantly increased risk for infective endocarditis was found after certain cardiovascular procedures (particularly coronary artery bypass grafting), procedures involving the skin and management of wounds, transfusion, dialysis, bone marrow puncture, and some endoscopies (particularly bronchoscopy). This large study “suggests that several invasive nondental medical procedures are associated with a markedly increased risk for infective endocarditis,” the authors concluded.

The authors noted that the use of prophylactic antibiotics before procedures has been discouraged in recent years. They calculated that, based on the study, 476 patients undergoing high-risk medical procedures would need to receive antibiotics to prevent one case of infective endocarditis. If prophylactic antibiotics were more narrowly targeted at particularly high-risk procedures, the number needed to treat could be lower (83 for bronchoscopy, for example). These calculations are based on antibiotics providing perfect protection against infective endocarditis and so would not be entirely accurate in real-world practice, the authors cautioned.

The study results could also encourage improvement of aseptic measures before and during procedures, consideration of the costs and benefits of elective procedures for patients at high risk, and earlier identification of infective endocarditis after procedures, the study authors said.

An accompanying editorial comment cautioned that observational data do not prove causality but agreed that the study “reopens the debate on the role of invasive medical procedures as a trigger for infective endocarditis.” The editorialists recommended a response focused on infection avoidance. “At least for those procedures where sterility should be easy to achieve and maintain, the solution is more likely to lay with improved sterile technique, infection control procedures and identifying systematic approaches for reducing health care-associated bacteremia rather than necessarily advocating antibiotic prophylaxis,” they wrote.

Acute exacerbations of COPD associated with risk for acute cardiovascular event

Patients who experience an acute exacerbation of chronic obstructive pulmonary disease (COPD) may be at increased risk for a subsequent cardiovascular event, according to a recent study.

Researchers performed a case-series analysis of data from patients in three U.S. states from 2005 through 2011 who were at least 40 years of age and had an acute COPD exacerbation. The goal of the study was to determine whether an acute exacerbation was associated with acute cardiovascular event incidence at 30 days and one year. The primary outcome measure was a composite of an ED visit or nonelective hospitalization for an acute cardiovascular event (acute myocardial infarction, heart failure, atrial fibrillation, pulmonary embolism, and stroke). Incidence rate ratios (IRRs) were estimated for acute cardiovascular event incidence in the 30-day period before the index exacerbation and the 30 days afterward, as well as for the one-year period after the index exacerbation versus the one-year period before it. Study results were published online June 8, 2018, by the Journal of General Internal Medicine and appeared in the September 2018 issue.

The study included 362,867 patients who had an ED visit or hospitalization for an acute COPD exacerbation. Median age was 70 years, 57% of patients were women, and 71% were of non-Hispanic white ethnicity. The incidence of acute cardiovascular events was significantly higher in the 30 days postexacerbation versus the 30-day reference period (IRR, 1.34; P<0.001) and in the year postexacerbation versus the one-year reference period (IRR, 1.20; P<0.001). This association between an acute COPD exacerbation and an acute cardiovascular event persisted for each cardiovascular condition separately (P<0.05 for all).

The researchers noted that administrative data could have misclassified some hospitalizations and that the databases used did not include information on clinical variables such as chronic COPD severity, among other limitations. However, they concluded that an association exists between acute COPD exacerbation and increased incidence of a subsequent acute cardiovascular event at 30 days and one year.

“Our findings should encourage researchers to elucidate the mechanisms linking [acute exacerbation of COPD] to the development of cardiovascular events,” the authors wrote. “For clinicians, our data support an importance of [acute exacerbation of COPD] as an opportunity to implement cardiovascular prevention measures in this high-risk population.”

High D-dimer level on admission for heart failure may indicate higher short-term stroke risk

Patients with elevated D-dimer levels at admission for acute heart failure had increased short-term risk of ischemic stroke, according to a recent study.

The retrospective registry study included 721 consecutive patients hospitalized for acute heart failure between January 2013 and May 2016 at a single center in Japan. All had their plasma D-dimer levels measured on admission. The patients' mean age was 76 years, 60% were men, and 54% had atrial fibrillation. The mean left ventricular ejection fraction was 38%, and the median length of hospitalization was 21 days. Compared to a normal D-dimer level of less than 1.0 µg/mL, the patients' median level on admission was 2.1 µg/mL (interquartile range, 1.1 to 4.2 µg/mL). Results were published by Stroke on June 7, 2018, and appeared in the July 2018 issue.

An ischemic stroke occurred during hospitalization in 18 patients (2.5%), and 16 patients (2.2%) had an ischemic stroke within 30 days. The study found the optimal D-dimer cutoff value for the risk of stroke in the hospital or within 30 days was 3.5 µg/mL. No patients with a D-dimer level less than the reference limit of normal (1.0 µg/mL) had a stroke. A higher D-dimer level on admission was an independent determinant of risk of in-hospital ischemic stroke even after adjustment for CHA2DS2-VASc score (odds ratio [OR], 2.29; 95% CI, 1.46 to 3.60; P<0.001) and major confounders, including age, atrial fibrillation, and antithrombotic therapy (OR, 2.31; 95% CI, 1.43 to 3.74; P<0.001). The results were similar in the subgroups of patients without atrial fibrillation (OR, 2.46; 95% CI, 1.39 to 4.54; P=0.002) and those not on antithrombotic therapy (OR, 2.79; 95% CI, 1.53 to 5.57; P<0.001) and when 30-day risk of stroke was the outcome.

The results suggest that a high D-dimer level at admission may be useful to identify patients with acute heart failure who have high thromboembolic risk, and conversely, that a normal level may exclude short-term risk of stroke, the study authors said. They noted that the study found high risk of thromboembolism in the immediate period after an acute heart failure event and thus, “risk stratification for short-term ischemic stroke events is strongly warranted for the management of hospitalized patients with [acute heart failure].”

Current guidelines do not recommend routine antithrombotic therapy for patients with heart failure without atrial fibrillation, said the authors, who suggested that biomarkers like D-dimer could potentially be used to identify patients who would benefit. Limitations of the study include that it was conducted at a single center with a relatively small sample size and that it was retrospective, with the use of antithrombotic therapy decided by the treating physicians.

Many patients report avoidable sleep disruptions in the hospital, Dutch survey finds

The majority of hospital patients reported being awakened during the night by external causes, and overall sleep duration was lower than at home, a recent Dutch study found.

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Image by Getty Images

The observational study was conducted using a flash-mob research method in 39 hospitals in the Netherlands on Feb. 22, 2017. Surveys asking for a comparison of the quantity and quality of last night's sleep in the hospital versus habitual sleep at home the month before hospitalization were collected from 2,005 patients (median age, 68 years; interquartile range, 57 to 77 years). The surveys used the Consensus Sleep Diary and the Dutch-Flemish Patient-Reported Outcomes Measurement Information System Sleep Disturbance item bank. Results were published by JAMA Internal Medicine online on July 26, 2018, and in the September 2018 print issue.

Patients reported sleeping 83 minutes less in the hospital than at home (95% CI, 75 to 92 minutes; P<0.001). Their mean number of nocturnal awakenings was 2.0 (95% CI, 1.9 to 2.1) at home versus 3.3 (95% CI, 3.2 to 3.5) in the hospital (P<0.001). The patients woke up 44 minutes earlier than they habitually did at home. More than two-thirds (70.4%) reported having been awakened by external causes, a third (35.8%) of which involved hospital staff. The most reported sleep-disturbing factors were noise of other patients, medical devices, pain, and toilet visits.

“Most of the sleep-disturbing factors found in our study seem easy to address by incorporating simple changes in nightly hospital routines,” the study authors said. Interventions such as dimmed hallway lights, silent footwear, remote alarms, earplugs, and eye masks can minimize noise and light disturbances, the authors noted. In addition, changing the timing of nursing activities, avoiding unnecessary procedures overnight, and minimizing continuous overnight IV drips and afternoon diuretics could potentially help and should be tested in prospective studies, the authors said.

They did note limitations to the study, including that almost one-third of surveyed patients had to be excluded due to missing data, including 41 patients who reported not to have slept at all. In addition, some patients weren't surveyed because they had delirium or cognitive problems or were asleep when the questionnaires were distributed.

An accompanying commentary cautioned that the study's unblinded questionnaires increased the risk of reporting bias but said the results “build a compelling case” for changing hospital culture to minimize sleep disruption. The editorialists offered a list of interventions to decrease sleep disruptions in the hospital.

Omitting ACE inhibitor before surgery reduced intraoperative hypotension, study finds

Omitting patients' usual angiotensin-converting enzyme (ACE) inhibitor dose prior to surgery reduced intraoperative hypotension, a recent study found.

The trial included 275 patients who had been taking an ACE inhibitor for at least six weeks before noncardiac, nonvascular surgery at a single academic medical center. They were randomized to either receive their usual dose before surgery (the continuation group, n=138) or have it omitted (the omission group, n=137). The primary outcome was intraoperative hypotension, defined as a systolic blood pressure (SBP) under 80 mm Hg. Results were published by the Journal of Hospital Medicine on July 25, 2018, and appeared in the October 2018 issue.

The study found that intraoperative hypotension was significantly less frequent in the omission group than the continuation group (55% vs. 69%; relative risk [RR], 0.81; 95% CI, 0.67 to 0.97; P=0.03; number needed to harm, 7.5). Postoperative hypotension, defined as an SBP under 90 mm Hg, was also less frequent in the omission group (RR, 0.49; 95% CI, 0.28 to 0.86; P=0.02), although the authors noted that the study was not powered to measure postoperative outcomes. Postoperative hypertension, defined as an SBP above 180 mm Hg, was more frequent in the omission group than in the continuation group (RR, 1.95; 95% CI, 1.14 to 3.34, P=0.01).

Finding less intraoperative hypotension with omission of an ACE inhibitor before surgery is in accordance with previous randomized trials, the study authors said. “These findings, while at odds with current [American College of Cardiology/American Heart Association] guidelines, align with the findings of a meta-analysis on this subject and with recent literature,” they wrote.

The study had a number of limitations, including variation in which ACE inhibitor was given and the timing of the last dose before surgery, the authors said. The postoperative findings also conflict with some previous research and they were not associated with any change in adverse events, the authors noted. They called for future research in this area to include clinically important endpoints.

Reducing intraoperative hypotension will not necessarily reduce adverse events, an accompanying editorial said. The editorialist noted controversy and variation in guidelines and policies on perioperative management of renin-angiotensin inhibitors. “Overall, perioperative physicians should now adopt the standard approach of temporarily withdrawing renin-angiotensin inhibitor therapy 24 hours before major inpatient noncardiac surgery. Nonetheless, they should do so cautiously, recognizing that the data underpinning this strategy remain weak,” the editorial said.