Results showed that survival to discharge increased in both groups over the 15-year study period. For the on-hours group, it increased from 16 percent in 2000 to 25.2 percent in 2014, while in the off-hours group the increase was from 11.9 percent to 21.9 percent. However, survival during off-hours remained significantly lower compared with on-hours.

According to the researchers, poor survival during off-hours is likely due to several factors: changes to hospital staffing patterns during nights and weekends; physicians working nights and weekends providing coverage to patients with whom they may be less familiar; lower nurse-to-patient ratios during off-hours; and the impact of shift work, particularly during nighttime, which has been shown to affect psychomotor skills and performance of skilled activities, such as cardiopulmonary resuscitation.

In an editorial accompanying the study, Julia H. Indik, MD, PhD, FACC, writes we must analyze the systems of care in hospitals with the smallest gaps in survival between on- and off-hours. She explains that an analysis of these hospitals may identify system characteristics that allow for the design and testing of future system protocols for the in-hospital cardiac arrest patient.

“A gap still remains for survival for cardiac arrests that occur at night or on a weekend. To close this gap will require that we identify the barriers so that new hospital protocols can be made. Time is of the essence,” Indik writes.

Ofoma UR, Basnet S, Berger A, et al. J Am Coll Cardiol 2018;71:402-11.

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A total of 196 ECGs from among 127 patients were analyzed. The mechanism was macro-reentry in 57 percent and centrifugal activity in 43 percent of cases. Among the former, reentry utilizing the left atrial roof and mitral isthmus was the most common. An isoelectric interval of >80 ms between P waves in all 12 leads was more prevalent in centrifugal vs. macro-reentrant tachycardias (47 percent vs. 24 percent; positive predictive value, 60 percent). However, the absence of such an interval was more helpful in distinguishing large vs. small circuits/focal activity (78 percent vs. 22 percent).

Negative P waves in the inferior leads, although present in only 15 percent of cases, were consistent with counterclockwise (CCW) typical atrial flutter. However, only 27 percent of such ECGs demonstrated classic saw-tooth activity. A gradual transition across the precordium (positive to negative) was compatible with CCW typical atrial flutter (sensitivity, 59 percent), as opposed to an abrupt transition, which was consistent with a reentry around the mitral annulus (sensitivity, 30 percent). Subtle, negative notching at the onset of an upright P wave in the inferior leads pointed toward reentry around the mitral annulus in a clockwise manner (sensitivity, 25 percent).

“Our study shows that the interpretation of the surface electrocardiogram post-LA [left atrial] ablation bears major limitations that hinder its use,” the authors write. “We could identify a few unique ECG characteristics that could still be used to help identify the mechanism of two of the most frequent macro–re-entries after PsAF [persistent AFib] ablation, namely, perimitral and peritricuspid AT. Knowledge of these features may allow more appropriate procedural planning and guide the initial mapping strategy.”

Pascale P, Roten L, Shah AJ, et al. JACC Clin Electrophysiol 2018;4:33-45.

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Infarct mice exhibited elevated myocardial translocator protein (TSPO) signal at one week vs. sham mice (percent injected dose per gram: 8.0 vs. 4.8; p < 0.001), localized to activated CD68+ inflammatory cells in the infarct. Early TSPO signal predicted subsequent left ventricular remodeling at eight weeks (rpartial = –0.687; p = 0.001). In parallel, brain TSPO signal was elevated at one week (1.7 vs. 1.4 for sham; p = 0.017), localized to activated microglia. After interval decline at four weeks, progressive heart failure precipitated a second wave of neuroinflammation (1.8; p = 0.005). TSPO was concurrently upregulated in remote cardiomyocytes at eight weeks (8.8; p < 0.001) without inflammatory cell infiltration, suggesting mitochondrial impairment. Angiotensin-converting enzyme inhibitor treatment lowered acute inflammation in the heart (p = 0.003) and brain (p = 0.06) and improved late cardiac function (p = 0.05). There was elevation of cardiac TSPO signal in the infarct territory, paralleled by neuroinflammation vs. controls.

The authors found that acute MI leads to an early inflammatory response, which stimulates adverse left ventricular remodeling and triggers brain microglia activation in a biphasic pattern. They write that a systems-based, multiorgan molecular imaging strategy may assist in the development of targeted anti-inflammatory therapies that may benefit both systems by providing risk assessment, identifying therapeutic target expression and monitoring intervention effectiveness.

In an accompanying editorial comment, Y. Chandrashekhar, MD, FACC, and Jagat Narula, MD, PhD, FACC, write, “Even though human studies have failed to provide evidence for cardioprotection with TSPO ligands, TSPO still remains an important diagnostic marker for multisystem inflammation, given its central role in inflammation management in activated macrophages and microglia. The current study also shows the tremendous potential of novel imaging to study multiorgan systems pathology… Given the difficulty in sampling specific biomarkers or clinical tissue from multiple involved organ systems, whole-body molecular and cellular imaging can provide a global understanding of information tracking the disease across networks and hopefully allow translation of accrued understanding into endpoints for clinical trials, or even targeted therapeutics.”

Thackeray JT, Hupe HC, Wang Y, et al. J Am Coll Cardiol 2018;71:263-75.

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Primary patient outcome in BIOSTAT-CHF was the first occurrence of all-cause mortality or HF-related hospitalization. Survival time was calculated from date of inclusion in BIOSTAT-CHF to date of death/HF hospitalization or date of censoring. The study authors compared clinical outcomes between three theoretical treatment scenarios: A) all patients uptitrated to >50 percent of recommended doses; B) patients uptitrated using a biomarker-based treatment selection model; and C) no patient uptitrated to >50 percent of recommended doses. Only patients who were followed for three months or less were included in the present analysis. A multivariable Cox regression was performed using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths and/or HF hospitalizations at 24 months for all three scenarios.

In 1,802 patients with available biomarkers, the rates of estimated death/hospitalization with ACE inhibitor/ARB were 16 percent, 16 percent and 26 percent, respectively, for the uptitration scenarios A, B and C. Patients not benefitting from ACE inhibitor/ARB uptitration were younger, more frequently smokers, with less atrial fibrillation; they had higher hemoglobin and blood urea nitrogen (BUN) levels, but lower heart rate and NT-proBNP levels.

For the beta-blocker uptitration, the rates of estimated death/hospitalization were 23 percent, 19 percent and 24 percent for scenarios A, B and C. For MRA uptitration, these rates were 12 percent, 11 percent and 24 percent, respectively.

Patients not benefitting from beta-blocker uptitration were older, leaner, and more frequently smokers or former smokers. They had less ischemic HF, but more myocardial infarctions and other comorbidities. And they had significantly higher LVEF, NT-proBNP, BUN and creatinine levels, and lower diastolic blood pressure, heart rate, hemoglobin and estimated glomerular filtration rate.

If uptitration was successful in all patients using the scenarios, the estimated number of events per 100-treated patients that could be prevented at 24 months was 9.8 with ACE inhibitor/ARB treatment, 1.3 with beta-blocker and 12.3 with MRA treatment. Biomarker-guided uptitration provided similar results. The estimated number of events per 100-treated patients that could be prevented at 24 months was 9.9 with ACE inhibitor/ARB, 4.7 with beta-blocker, and 13.1 with MRA.

The authors estimate that one in 50, one in three and one in eight patients would not benefit from ACE inhibitor/ARB, beta-blocker or MRA uptitration, but that their mortality/hospitalization hazards would not increase much due to uptitration.

“Because of the nature of this study, and the small differences between biomarker-based treatment choice and the scenario in which all patients would have been successfully uptitrated, we suggest that uptitration should always be attempted in heart failure patients, which should lead to improved treatment of life-saving therapies across Europe,” they conclude.

Ouwerkerk W, Zwinderman AH, Ng LL, et al. J Am Coll Cardiol 2018;71:386-98.

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