Should we screen for coronary artery disease in asymptomatic chronic dialysis patients?

The hemodialysis population is characterized by a high prevalence of ‘asymptomatic’ coronary artery disease (CAD), which should be interpreted differently from asymptomatic disease in the general population. A hemodynamically significant stenosis may not become clinically apparent owing to impaired exercise tolerance and autonomic neuropathy. The continuous presence of silent ischemia may cause heart failure, arrhythmias, and sudden death. Whether revascularization of an asymptomatic dialysis patient improves outcome remains a moot point, although several observational studies and one small RCT suggest a benefit. It can therefore be defended to screen asymptomatic dialysis patients for CAD. A number of noninvasive screening tests are available, but none has proved equally practical and reliable in the dialysis population as in the general population. Myocardial perfusion scintigraphy (MPS) before and after a pharmacological stress such as dipyridamole can reveal both ischemia and myocardial scarring. When compared with coronary angiography, low sensitivities were reported and attributed to impaired vasodilation to dipyridamole in dialysis patients. A more likely explanation is that not every anatomical stenosis will lead to impaired coronary blood flow on MPS. Numerous studies have shown an incremental prognostic value of dipyridamole-MPS over clinical data for prediction of adverse cardiac events, in some studies even over coronary angiography. Pending the availability of high-quality evidence, in our opinion asymptomatic dialysis patients could undergo dipyridamole-MPS, followed by coronary angiography in case of an abnormal scan. This combined physiological and anatomical evaluation of the coronary circulation allows us to determine which coronary stenosis is clinically relevant and therefore should be revascularized

Comparison of the prognostic value of dipyridamole and dobutamine myocardial perfusion scintigraphy in hemodialysis patients

Screening for coronary artery disease (CAD) in hemodialysis patients is hampered by contraindications and/or limitations of the available techniques in this population. Myocardial perfusion scintigraphy (MPS) using dipyridamole has been considered inaccurate due to abnormally high basal levels of adenosine in uremia that could blunt the vasodilatory response. Since dobutamine may be more reliable, we directly compared the two in patients on hemodialysis. We performed MPS at rest and after separate dipyridamole or dobutamine stress in 121 chronic hemodialysis patients. More numerous, larger, and more intense reversible lesions were induced with dobutamine than with dipyridamole, mainly in the anteroseptal segments. Reversibility with dipyridamole but not dobutamine MPS was independently and strongly related with mortality associated with CAD and with fatal and non-fatal CAD. We hypothesize that the chronotropic action of dobutamine induced alterations of wall motion, leading to spurious perfusion defects, not unlike artifacts seen with left bundle branch block. Our study shows that even though dobutamine induced more pronounced myocardial ischemia than dipyridamole in chronic hemodialysis patients, dipyridamole MPS more accurately identifies patients at high risk for subsequent cardiac death or non-fatal CAD than dobutamine

Cardiac myosin activation with omecamtiv mecarbil in systolic heart failure

BACKGROUND The selective cardiac myosin activator omecamtiv mecarbil has been shown to improve cardiac function in patients with heart failure with a reduced ejection fraction. Its effect on cardiovascular outcomes is unknown. METHODS We randomly assigned 8256 patients (inpatients and outpatients) with symptomatic chronic heart failure and an ejection fraction of 35% or less to receive omecamtiv mecarbil (using pharmacokinetic-guided doses of 25 mg, 37.5 mg, or 50 mg twice daily) or placebo, in addition to standard heart-failure therapy. The primary outcome was a composite of a first heart-failure event (hospitalization or urgent visit for heart failure) or death from cardiovascular causes. RESULTS During a median of 21.8 months, a primary-outcome event occurred in 1523 of 4120 patients (37.0%) in the omecamtiv mecarbil group and in 1607 of 4112 patients (39.1%) in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.86 to 0.99; P = 0.03). A total of 808 patients (19.6%) and 798 patients (19.4%), respectively, died from cardiovascular causes (hazard ratio, 1.01; 95% CI, 0.92 to 1.11). There was no significant difference between groups in the change from baseline on the Kansas City Cardiomyopathy Questionnaire total symptom score. At week 24, the change from baseline for the median N-terminal pro-B-type natriuretic peptide level was 10% lower in the omecamtiv mecarbil group than in the placebo group; the median cardiac troponin I level was 4 ng per liter higher. The frequency of cardiac ischemic and ventricular arrhythmia events was similar in the two groups. CONCLUSIONS Among patients with heart failure and a reduced ejection, those who received omecamtiv mecarbil had a lower incidence of a composite of a heart-failure event or death from cardiovascular causes than those who received placebo. (Funded by Amgen and others; GALACTIC-HF ClinicalTrials.gov number, NCT02929329; EudraCT number, 2016 -002299-28.)