Featured topics and Editors’ Picks from all of ACC’s JACC Journals. Central Apnea Associated with Worse Outcomes in Systolic HF In patients with systolic heart failure (HF), central apneas occur throughout a 24-hour period and are associated with neurohormonal activation, ventricular arrhythmic burden and worse prognosis, according to research published in the Journal of the American College of Cardiology. Michele Emdin, MD, PhD, et al., enrolled 525 patients with systolic HF and impaired left ventricular systolic function receiving stable guideline-recommended treatment. All patients underwent 24-hour continuous polygraphic recording, including electrocardiography, respiration by chest and abdominal inductance plethysmography belts, nasal airflow detection and oxygen saturation (SaO2). During the 24-hour period, normal breathing increased in the daytime, the obstructive apnea prevalence decreased and the central apnea prevalence remained predominant. The prevalence of central apnea at night, during the day and throughout the 24-hour period was 69.1 percent, 57.0 percent and 64.8 percent, respectively, whereas the prevalence of obstructive apnea was 14.7 percent, 5.9 percent and 12.7 percent, respectively. During a median 34-month follow-up, 50 cardiac deaths occurred. Episodes of central apnea were associated with neurohormonal activation, ventricular arrhythmic burden and systolic/diastolic dysfunction. Nighttime, daytime and 24-hour moderate-to-severe central apneas were associated with increased cardiac mortality. The researchers state the findings may at least partially explain the failure of previous therapeutic attempts, such as continuous positive airway pressure or adaptive servoventilation, because targeting only “sleep” apnea may be insufficient in patients who manifest central apneas all day. Further, the findings could explain the prognostic benefit and decrease in central apnea incidence associated with adjustment or upgrade of HF therapy. These treatments likely act on the pathophysiological triggers of central apnea and over the entire circadian period, thus including the subset at major risk. In an editorial comment, John S. Floras, MD, Dphil, FACC, writes, “although the present data may conflate central apnea, obstructive apnea, and normal breathing pauses plus events during wakefulness and sleep, the concept of a 24-hour central apnea burden with prognostic significance, as presented by Emdin et al., is a hypothesis sufficiently intriguing and so potentially transformational that it merits further independent investigation.” Emdin M, Mirizzi G, Giannoni A, et al. J Am Coll Cardiol 2017;70:1351-64. Diabetes in AFib Increases Symptoms, Mortality, Hospitalizations Patients with atrial fibrillation (AFib) and diabetes have worse AFib symptoms, lower quality of life, higher mortality and higher hospitalization rates than AFib patients without diabetes, according to a study published in the Journal of the American College of Cardiology. Justin B. Echouffo-Tcheugui, MD, PhD, et al., enrolled 9,479 adults with AFib from the ORBIT-AF registry for this prospective, observational cohort study with a mean follow-up of 2.4 years. Diabetes was diagnosed in 2,874 (29.5 percent) AFib patients. Patients with diabetes vs. those without had a higher risk of stroke and bleeding (p < 0.001 for both). They also had greater functional impairment, more dyspnea and fatigue and lower overall median Atrial Fibrillation Effect on Quality of Life scores. The use of anticoagulants was greater in diabetes. On multivariate analysis, diabetes was associated with a higher risk of all-cause death, both among patients <70 years (adjusted hazard ratio [HR], 1.63; p = 0.033) and those ≥70 years of age (adjusted HR, 1.25; p = 0.001). Additionally, diabetes was associated with a significantly increased risk of cardiovascular death, non-cardiovascular death, sudden cardiac death, all-cause and cardiovascular hospitalization, and non-cardiovascular, non-bleeding hospitalization. The investigators did not find an increased risk of thromboembolic events, AFib progression or incident heart failure with diabetes. “Among patients with AFib in this nationwide cohort, the prevalence of diabetes mellitus was 30 percent, emphasizing the importance of diabetes screening in patients diagnosed with AFib,” the authors write. “Future studies are warranted to explore ways to mitigate this mounting problem, which could exponentially worsen in the years to come given the growing diabetes epidemic,” the authors conclude. Zachary T. Bloomgarden, MD, et al., comment that some of the findings “offer grounds for optimism.” The observation that patients with diabetes were more likely to receive anticoagulation may explain the lack of a difference in thromboembolic events; the absence of bleeding complications suggests a favorable benefit-to-risk balance with anticoagulation therapy. “The study offers perhaps the most comprehensive assessment of the management and outcomes of patients with concomitant diabetes and AFib to date, increases our understanding of the cardiovascular consequences of diabetes, and may influence our approach to the diabetic patient who develops AFib,” they write. Echouffo-Tcheugui JB, Shrader P, Thomas L, et al. J Am Coll Cardiol 2017;70:1325-35. Short-Term Mortality Lower With Type 2 MI Versus Type 1 MI Patients with type 2 myocardial infarction (T2MI) without underlying coronary artery disease (CAD) have substantially lower event-related mortality compared with patients with T2MI without CAD, reports a study published in the Journal of the American College of Cardiology. Thomas Nestelberger, MD, et al., in this secondary analysis of the APACE trial, assessed the effect of the definition of T2MI on its incidence, treatment and event-related mortality among adults presenting with symptoms suggestive of MI from the time of presentation to 90-days follow-up. Type 1 MI (T1MI) was defined as spontaneous MI related to ischemia due to a primary coronary event. T2MI-2007 was defined using the second universal definition of MI published in 2007 as MI secondary to ischemia with known or newly diagnosed CAD. T2MI-2012 was defined using the third universal definition published in 2012 as MI secondary to ischemia but the presence of CAD was not required. Patients meeting the T2MI-2012 definition but not the T2MI-2007 definition were reclassified and analyzed separately (T2MI-2012-reclassified). T2MI-2012 included T2MI-2007 plus T2MI-2012-reclassified. The results showed that of 4,015 patients eligible for analysis, 17 percent had T1MI, 2.8 percent had T2MI-2007 and 6 percent had T2MI-2012-reclassified. High-sensitivity cardiac troponin (hs-cTn) levels were highest in patients with T1MI and lowest in those with T2MI-2012-reclassified. Ninety-day mortality was significantly lower in patients with T2MI-2012-reclassified (0 percent) vs. patients with T2MI-2007 (0 percent; log rank test, p = 0.03) and T1MI (3.7 percent; log rank test, p = 0.01). This study showed that patients reclassified with cardiomyocyte injury due to supply-demand mismatch who do not have underlying CAD (T2MI-2012-reclassified) have substantially lower event-related mortality compared with patients with CAD (T2MI-2007). “Their classification as ‘MI’ may be misleading and should be reconsidered,” the authors write. In a related editorial, James L. Januzzi Jr., MD, FACC, et al., discuss several caveats. “Though we agree in principle that T2MI without CAD likely has a more benign course, we do not support reconsideration of their diagnosis,” they write. “We propose investigating T2MI using a phenotypespecific approach…Only with a clear understanding of the spectrum of T2MI can we approach the development of treatment options.” Nestelberger T, Boeddinghaus J, Badertscher P, et al. J Am Coll Cardiol 2017;70:1558-68. Secondary Prevention Outcomes and Adherence to Multiple Therapies After AMI Beta-blockers may have limited additional benefit in patients taking angiotensinconverting enzyme inhibitors (ACEI)/angiotensin II receptor blockers (ARB) and/or statins after acute myocardial infarction (AMI). Mortality rates were similar in patients adherent only to ACEI/ ARBs and statins and in patients adherent to all three therapies post AMI, according to a study published in the Journal of the American College of Cardiology. Led by Maarit J. Korhonen, LicSci (Pharm), PhD, et al., the study used the Centers for Medicare and Medicaid Services Medicare Chronic Condition Data Warehouse to identify 90,869 patients (median age, 77 years) who had a prescription for all three therapies (ACEI/ARB, statins and beta-blockers) and survived 180 days or more after being hospitalized for AMI between 2008 and 2010. The authors measured therapy adherence by proportion of days covered (PDC) of the 180 days after being discharged, classifying adherent as 80 percent PDC and non-adherent as <80 percent PDC. Mortality follow-up covered the 18 months following the 180-day post-discharge period. More than half of patients (51.5 percent) were non-adherent to one or more preventive therapies. Of these, 31 percent did not take ACEI/ARBs, 24 percent beta-blockers and 23 percent did not take statins. Ten percent of the total study population died during follow-up. The mortality rate was highest in patients non-adherent to all three therapies (hazard ratio [HR], 1.65), followed by those who only took beta-blockers (HR, 1.32). “Clinical uncertainties exist as to the clinical impact of adherence to some therapies versus all three in the long-term. In clinical practice, this is a particularly challenging issue for older adults with multiple morbidities and polypharmacy,” write the authors. “We found markedly higher mortality risk for being adherent to beta-blockers only among patients with diabetes or dementia than among patients without these conditions.” “It’s safe to say that adherence to medications post-MI is in dire need of an infusion of ‘stickiness,’” note Eric D. Peterson, MD, MPH, FACC, and Ann Marie Navar, MD, PhD. In a related editorial, they commend the authors on raising a provocative hypothesis, yet underline the unlikeliness that a large randomized trial would ever occur to confirm the results. Instead, they explore patient education tools, electronic reminders and more, emphasizing the importance of physician-patient conversations and the impact compelling messaging would have on overall behavioral change. “The field of medicine should learn from their colleagues in marketing, behavioral economics, and social science to identify which levers are most effective for improving patient medication adherence, and then test the impact of moving those levers in large outcome trials.” Korhonen MJ, Robinson JG, Annis IE, et al. J Am Coll Cardiol 2017;70:1543-54.
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