Recent advances in the diagnosis and treatment of acute myocardial infarction

Table 1 Causes of troponin elevation

System	Causes of troponin elevation
Cardiovascular	Acute aortic dissection
	Arrhythmia
	Medical ICU patients
	Hypotension
	Heart failure
	Apical ballooning syndrome
	Cardiac inflammation
	Endocarditis, myocarditis, pericarditis
	Hypertension
	Infiltrative disease
	Amyloidosis, sarcoidosis, hemochromatosis, scleroderma
	Left ventricular hypertrophy
Myocardial injury	Blunt chest trauma
	Cardiac surgeries
	Cardiac procedures
	Ablation, cardioversion, percutaneous intervention
	Chemotherapy
	Hypersensitivity drug reactions
	Envenomation
Respiratory	Acute PE
	ARDS
Infectious/immune	Sepsis/SIRS
	Viral illness
	Thrombotic thrombocytopenic purpura
Gastrointestinal	Severe GI bleeding
Nervous system	Acute stroke
	Ischemic stroke
	Hemorrhagic stroke
	Head trauma
Renal	Chronic kidney disease
Endocrine	Diabetes
	Hypothyroidism
Musculoskeletal	Rhabdomyolysis
Integumentary	Extensive skin burns
Inherited	Neurofibromatosis
	Duchenne muscular dystrophy
	Klippel-Feil syndrome
Others	Endurance exercise
	Environmental exposure
	Carbon monoxide, hydrogen sulfide

GI: Gastrointestinal; ICU: Intensive care unit; PE: Pulmonary embolus; ARDS: Acute respiratory distress syndrome; SIRS: Systemic inflammatory response syndrome.

Table 2 Electrocardiogram manifestations of acute myocardial ischemia (in absence of left ventricular hypertrophy and left bundle branch block)

ST elevation

New ST elevation at the J point in two contiguous leads with the cut-points:

≥ 0.1 mV in all leads other than leads V2–V3 where the following cut points apply: ≥ 0.2 mV in men ≥ 40 yr; ≥ 0.25 mV in men < 40 yr, or ≥ 0.15 mV in women

ST depression and T wave changes

New horizontal or down-sloping ST depression ≥ 0.05 mV in two contiguous

leads and/or T inversion ≥ 0.1 mV in two contiguous leads with prominent R wave or R/S ratio > 1

Table 3 Third universal classification of myocardial infarction

Type 1: Spontaneous MI

Spontaneous MI due to atherosclerotic plaque rupture, ulceration, fissuring, erosion, or dissection with resulting intraluminal thrombus in one or more of the coronary arteries leading to decreased myocardial blood flow or distal platelet emboli with ensuing myocyte necrosis. The patient may have underlying severe CAD, non-obstructive coronary disease or no CAD

Type 2: MI secondary to an ischemic imbalance

Myocardial injury with necrosis occurs due to conditions other than CAD that contribute to an imbalance between myocardial oxygen supply and/or demand such as coronary endothelial dysfunction, coronary artery spasm, coronary embolism, tachycardia-bradycardia arrhythmias, anemia, respiratory failure, hypotension, and hypertension

Type 3: MI resulting in death when biomarker values are unavailable

Cardiac death with symptoms suggestive of myocardial ischemia and presumed new ischemic ECG changes or new LBBB, but death occurs before blood samples can be obtained, before cardiac troponins biomarkers rise, or when cardiac biomarkers were not collected

Type 4A: MI related to percutaneous coronary intervention

MI associated with PCI is defined by elevation of cTn values greater than five times the 99th percentile upper normal reference limit (URL) in patients with normal baseline values (< 99th percentile URL) or a rise of cTn values by > 20% if the baseline troponins are elevated and are stable or falling. In addition one of the following criterion are required: (1) symptoms suggestive of myocardial ischemia; (2) new ischemic ECG changes or new LBBB; (3) angiographic loss of patency of a major coronary artery or a side branch or persistent slow- or no coronary flow or coronary embolization; or (4) demonstration with imaging of a new loss of viable myocardium or new regional wall motion abnormality

Type 4B: MI related to stent thrombosis

MI associated with stent thrombosis detected by coronary angiography or autopsy in the presence of myocardial ischemia with a rise and/or fall of troponin biomarkers. One troponin measurement should be above the 99th percentile UR

Type 4C: MI related to restenosis

MI associated with restenosis defined as ≥ 50% stenosis or a complex lesion demonstrated at coronary angiography after (1) initial successful stent deployment; or (2) dilatation of a coronary artery stenosis with balloon angioplasty. These coronary angiographic changes should be associated with an increase and/or decrease of cTn values > 99th percentile URL and no other significant obstructive CAD

Type 5: MI related to coronary artery bypass grafting

MI associated with CABG is defined by elevation of cardiac troponins greater than ten times the 99th percentile URL in patients with normal baseline cTn values (< 99th percentile URL). In addition, one of the following should be present: (1) new pathological Q waves or new LBBB; or (2) angiographic documented new graft or new native coronary artery occlusion; or (3) new loss of viable myocardium or new regional wall motion abnormality as shown by an imaging modality

Adapted from Thygesen et al[14]. MI: Myocardial infarction; CAD: Coronary artery disease; PCI: Percutaneous coronary intervention; cTn: Cardiac troponin; CABG: Coronary artery bypass grafting; LBBB: Left bundle branch block.

Table 4 Proposed definition of clinically relevant myocardial infarction after both percutaneous coronary intervention and coronary artery bypass grafting procedures

In patients with normal baseline CK-MB	The peak CK-MB measured within 48 h of the procedure rises to ≥ 10 × the local laboratory ULN, or to ≥ 5 × ULN with new pathologic Q-waves in ≥ 2 contiguous leads or new persistent LBBB, OR in the absence of CK-MB measurements and a normal baseline cTn, a cTn (I or T) level measured within 48 h of the PCI rises to ≥ 70 × the local laboratory ULN, or ≥ 35 × ULN with new pathologic Q-waves in ≥ 2 contiguous leads or new persistent LBBB
In patients with elevated baseline CK-MB (or cTn) in whom the biomarker levels are stable or falling	The CK-MB (or cTn) rises by an absolute increment equal to those levels recommended above from the most recent pre-procedure level
In patients with elevated CK-MB (or cTn) in whom the biomarker levels have not been shown to be stable or falling	The CK-MB (or cTn) rises by an absolute increment equal to those levels recommended above plus new ST-segment elevation or depression plus signs consistent with a clinically relevant MI, such as new onset or worsening heart failure or sustained hypotension

ULN: Upper limit of normal; MI: Myocardial infarction; cTn: Cardiac troponin.

Table 5 Bone marrow and circulating progenitor cells in coronary artery disease patients

Ref.	n	Randomize	Timepost PCI and/or MI	Cell dose	Injection route	Baseline LVEF	LVEFchange	Duration	Other findings
Assmus et al[215]	92	Yes	2348-2470 d	22 ± 106 CPC 205 ± 110 × 106 BMC	IC	CPC 39% ± 10% BMC: 41% ± 11%	CPC -0.4% BMC 2.90%	3 mo	Pts with previous MI; ↑ LVEF in BMC but not CPC
Bartunek et al[216]	35	Cohort	10 d	12.6 ± 2.2 × 106	IC	45% ± 2.5%	7%	4 mo	↑ LV regional function, perfusion; restenosis ↑
Chen et al[217]	69	Yes	18.4 ± 0.5 d	8-10 × 109	IC	49% ± 9%	18%	6 mo	↑ LVEF by ventriculogram ↑ perfusion; ↓ ESV
Erbs et al[218]	26	Yes	225 ± 87 d	69 ± 14 × 106	IC	51.7% ± 3.7%	7.20%	3 mo	Pts with chronic CAD occlusion Rxed with CPC; ↓ EF by MRI; infarct size 16%
Ge et al[219]	20	Yes	1 d	39 ± 22 × 106	IC	53.8% ± 9.2%	4.80%	6 mo	↑ Perfusion by SPECT
Hendrikx et al[220]	20	Yes	217 ± 162 d	60 ± 31 × 106 IM	IM	42.9% ± 10.3%	5%	4 mo	CABG in Pts with previous CAD ↑ Regional but not global LV function; 6/9 with induced ventricular tachycardia
Janssens et al [221]	67	Yes	1 d	172 × 106	IC	48.5 ± 7.2	3.30%	4 mo	↓ Infarct size
Kang et al[222]	96	Yes	< 14 d AMI; > 14 d OMI	1-2 × 109	IC	52.0 ± 9.9	5.10% AMI	6 mo	G-CSF for 3 d; ↓ ESV and infarct size in AMI; = EF, ESV and infarct size in OMI
Katritsis et al[223]	22	Cohort	224 ± 464 d	2-4 × 106	IC	39.7% ± 9.3%	1.60%	4 mo	↑ Regional but not global LV function
Lunde et al[224,225]	100	Yes	6 ± 1.3 d	68 × 106 (median) 54-130 × 106	IC	41.3 ± 11.0	=	6-12 mo	↑ LVEF in treated and controls; = EDV and infarct size
Meyer et al[226]	60	Yes	4.8 ± 1.3	24.6 ± 9.4 × 108	IC	50 ± 10	5.90%	18 ± 6 mo	↑ LVEF by MRI significant at 6 but not 18 mo
Mocini et al[227]	36	Cohort	AMI < 6 mo	292 ± 232 × 106 IM	IM	46% ± 6%	5%	3-12 mo	CABG in all; troponin increased
Perin et al[228]	20	Cohort	ICM	25.5 ± 6.3 × 106	IM Trans-Endo-cardial	30% ± 6%	5.10%	12 mo	LVEF = Controls; ↑ LV perfusion ↑ Exercise
Ruan et al[229]	20	Yes	Approximately 1 d	NR	IC	53.5% ± 5.8%	5.80%	6 mo	↑ LV segmental contraction
Schächinger et al[230,231]	204	Yes	3-8 d	2.4 × 108	IC	48.3% ± 9.2%	6%-7%	4-12 mo	↑ EF when Rx > 4 d post MI and when EF ↑ ≤ 48.9; LV perfusion
Strauer et al[232]	20	Cohort	5-9 d	2.8 ± 2.2 × 107 IM	IC	57% ± 8%	5%	3 mo	↑ Regional but not global LVEF; ↓ ESV and ↓ Infarct size
Li et al[234]	70	Yes	7 ± 5 d	7.3 ± 7.3 × 107	IC	50% ± 8.2%	7%	6 mo	G-CSF for 5 d; ↓ LV ESV, ↓ LV wall motion score

NR: Not recorded or equals no change; CPC: Circulating progenitor cells; BMC: Bone marrow cells; ICM: Ischemic cardiomyopathy; IC: Intracoronary injection; IM: Intramyocardial injection; AMI: Acute myocardial infarction; OMI: Old myocardial infarction; G-CSF: Granulocyte colony stimulating factor; ESV: LV end-systolic volume; SPECT: Single photon emission computer tomography. Adapted from Henning[213].

Table 6 Stem cells in the treatment of patients with acute myocardial infarction

Ref.	n	Random-ized	Timepost MI	Cell dose	Baseline	LVEF	Duration	Other findings
Strauer et al[232]	20	Cohort	8 d	2.8 ± 2.2 × 107	57% ± 8%	5%	3 mo	↑ Regional but not global LVEF ↓ LV ESV and infarct size
Bartunek et al[216]	35	Cohort	10 d	12.6 ± 2.2 × 106	45% ± 2.5%	7%	4 mo	↑ LV regional function, ↑ perfusion; ↑↑ restenosis
Li et al[234]	70	Yes	6 d	7.3 ± 7.3 × 107	50 ± 8.2	7%	6 mo	↓ LV ESV, LV wall motion score
Janssens et al[221]	67	Yes	1 d	172 × 106	48.5 ± 7.2	3.30%	4 mo	↓ Infarct size
Meyer et al[226] and Wollert et al[237]	60	Yes	4.8 d	24.6 × 108	50.0 ± 10.0	=	6-18 mo	↑ LVEF at 6 but not at 18 mo
Kang et al[222]	96	Yes	4 d	1-2 × 109	52.0 ± 9.9	5.1% AMI	6 mo	↓ LV ESV and infarction in acute MI; = ESV and = old MI
Lunde et al[224,225]	100	Yes	6 d	68 × 106	41.3 ± 11.0	=	6-12 mo	LVEF ↑ in treated and controls; = EDV and infarct size
Ge et al[219]	20	Yes	1 d	4 × 107	53.8 ± 9.2	4.80%	6 mo	↑ LV regional wall perfusion by SPECT
Meluzín et al[235,236]	66	Yes	5-9 d	107-108	42 ± 0.0	3-5	3-12 mo	↑ LVEF 3% @107↑ LVEF 5%-7% @ 108 3-12 mo
Schächinger et al[230,231]	204	Yes	3-8 d	2.4 × 108	48.3 ± 9.2	6-7	4-12 mo	↑ EF when Rx > 4 d post MI and when EF < 48.9%; ↑ LV perfusion

Adapted from Henning[213]. MI: Myocardial infarctions; LVEF: Left ventricular ejection fraction.