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Letters to the Editor
vation or cardiac MRI) was 7.6 g/dL (2.9-12.6 g/dL). Only 5 (7.2%) patients had a history of diabetes mellitus and (8.6%) patients had a family history of myocardial infarc- tion. A majority of these patients (n=57, 83%) had a his- tory of acute chest syndrome (ACS) (Table 1).
Median initial troponin level was 0.14 ng/dL (range, 0.01-38.09) and peak troponin of 0.44 ng/dL (range, 0.01- 19.97). Patients with troponin elevation were more likely to have acute chest syndrome (40% vs. 10%; P=0.02) and acute kidney injury (0% vs. 18%; P=0.0002). There was no difference in median Hb in both groups; however, the troponin elevation group tended to have lower platelet count (272 vs. 165 K/uL, P=0.007), higher lactate dehy- drogenase (LDH) level (392 vs. 498 U/L, P=0.37) (Table 2). In an expanded cohort of 239 patients with troponin measurement, 42 (18%) had elevated troponin-I at one or multiple instances. Troponin elevation significantly increased the likelihood of death with a hazard ratio of 2.6 (95% Confidence Interval [CI]: 1.4-4.9; P=0.0003).
There were 47 patients with cardiac MRI performed over the 10-year period for various indications, most common being chest pain and/or troponin elevation (n=26) and iron overload. CMD was present in 15 patients (32%), only five patients had normal CMR and the rest of them had other non-ischemic findings. There was no statistically significant difference between the CMD and non-CMD groups in terms of baseline charac- teristics, clinical or laboratory variables (Table 2). Cardiac catheterization showed no epicardial vessel obstruction in eight patients, one patient had triple vessel disease. Overall survival was similar in both groups (P=0.42; Figure 1). Patients were treated with the following med- ications either alone or in combination: low dose aspirin (n=9), long-acting nitrate (n=5), beta-blockers (n=4), or angiotensin-converting enzyme inhibitors (ACEI) (n=3), clopidogrel (n=1). One patient, a 33-year-old male, pre- sented with ST-elevation MI with a peak troponin-I level of 38.09 ng/dL, cardiac catheterization with clean coro- naries and microvascular disease on MRI was started on aspirin, clopidogrel, beta-blockers, and ACEI. Two patients received a simple transfusion, exchange transfu- sion was recommended in one patient but was deferred later due to clinical improvement.
In 22 patients with troponin level measurement within 30 days before cardiac MRI, troponin elevation predicted the presence of CMD with a sensitivity of 87.5% (95% CI: 47-100) and specificity of 57% (95% CI: 29-82). There was no correlation between the degree of troponin elevation and CMD, the difference between median baseline and peak troponin was similar in both groups (0.08 ng/mL, range, 0-25.92 in CMD vs. 0.07 ng/mL, range, 0-1.04 in non-CMD; P=0.31). After restricting the analysis to troponin elevation within 14 days prior, the proportion of CMD was higher in elevated troponin group in patients without ACS (n=14, 100% vs. 43%, P=0.07) or AKI (n=19, 73% vs. 50%, P=0.38).
Our study highlights the fact that myocardial injury and coronary microvascular disease is indeed prevalent in SCD. The presence of troponin elevation in 18% of the SCD patients suggests that they suffer some degree of myocardial injury when presenting with chest pain or in an acute crisis. This number differs from a previous report by Aslam et al., in which 6.2% patients had tro- ponin elevation. However, the sample size was smaller and a higher troponin cutoff (0.4 ng/mL vs. 0.11 ng/mL) was used.4 Since troponin-I is well-established to be a very sensitive and specific marker of ongoing myocardial injury,10 lower sensitivity and specificity in our cohort might be explained by the timing of the troponin testing.
Table 1. Patient characteristics. Variable
Sex Male
Female
Genotype SS
SC Sβ-thal
History of SCD related complications ACS
AVN
Stroke Retinopathy Leg ulcer PHT
Body Mass Index (kg/m2) Median (range)
Coronary artery disease related factors Diabetes mellitus
Chronic kidney disease
History of aspirin use
Family history of myocardial infarction
Indications for cardiac MRI
Chest pain and/or troponin elevation Iron overload
Cardiomyopathy
Arrhythmias†
Right atrial mass
Pulmonary stenosis
Right to left shunt
Unknown
Number, out of total 69 patients (%)
34 (19-67) ≤20 3(4)
Age (years) Median (range)
≤40 >40
45 (65) 21 (30)
35 (51)
34 (49)
51 (75) 11 (16) 6 (9)
57 (83) 25 (36) 17 (25) 10 (14) 5 (7)
22 (33) 23.9 (12.3-46.2)
5 (7) 14 (20) 19 (28) 6 (9)
26 11 2 3 1 1 1 1
SS: homozygous sickle cell with hemoglobin SS; SC: homozygous sickle cell with hemoglobin SC; Sβ-thal: sickle cell β thalassemia; SCD: sickle cell disease; ACS: acute chest syndrome; AVN: avascular necrosis; PHT: pulmonary hypertension. †included ventricular tachycardia and AV-nodal re-entrant tachycardia.
As it is not a provocative test, troponin-I will not capture chronic ischemic changes, infarct scaring, and impaired myocardial perfusion reserve unless there is acute ischemia leading to myocardial damage at the time of testing. These findings can be elicited by CMR with con- trast and stress testing with great precision and accuracy. Patients with CMD will have impaired perfusion reserve at rest and ischemia on stress testing, it may or may not translate into myocardial injury to cause troponin eleva- tion.
To our knowledge, this is the first study to assess the
effect of myocardial injury and CMD on mortality for
SCD patients. Myocardial injury was associated with a
2.6-fold increase in all-cause mortality and there was a
statistically insignificant trend towards lower survival in
the CMD group. These findings can be a potential expla-
nation of the high frequency of sudden death, especially
of cardiac cause, in otherwise healthy patients presenting
11
There is no randomized controlled data on coronary
in acute crisis. Myocardium in distress with underlying ischemia can act as an arrhythmogenic substrate leading to fatal arrhythmias.12
haematologica | 2021; 106(7)
2019