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Microvascular angina: an update on diagnosis and treatment
Jane S Titterington1, Olivia Y Hung1 & Nanette K Wenger*,1
ABSTRACT Many patients with chest pain who are relieved to learn that they have no obstructive stenoses at diagnostic angiography are misclassified as having noncardiac chest pain. Only recently have we developed the conceptual framework and diagnostic tools to understand that ischemic heart disease is not exclusively caused by obstructive coronary artery disease, but often has its origin in the microcirculation. This article will focus on the diagnosis and treatment of microvascular angina as a cause of myocardial ischemia in patients with abnormal but ‘normal appearing’ coronary arteries. KEYWORDS
Background ●●Scope of the problem
Cardiovascular disease remains the leading cause of mortality in the USA, accounting for one of every three deaths. It is estimated that there are more than 1 million myocardial infarctions (MIs) each year [1] . Following an MI, nearly a third of patients develop systolic heart failure within 5 years [2] . Chronic stable angina, now characteristically referred to as stable ischemic heart disease (SIHD), affects 7.8 million people in the USA, and more than 50% of them (4.1 million) are women [1] . Approximately half a million new cases of angina occur annually [1] . In addition to the substantial morbidity and mortality, there is a huge economic cost associated with coronary artery disease (CAD). The WISE study was undertaken in order to evaluate symptomatic myocardial ischemia in women, with particular interest paid to those with angina but no epicardial coronary artery stenosis [3] . In this cohort, 62% of women with myocardial ischemia at noninvasive testing had nonobstructive coronary disease, and of those, 20% required hospitalization for chest pain within 5 years of initial angiography [4] . Women with nonobstructive CAD undergo angiography almost twice as frequently as women with single-vessel disease and have similar levels of disability and a higher angina burdens [4] . The lifetime medical costs for a woman in the WISE study with nonobstructive CAD is estimated to be US$770,000 [4] . Nearly half of patient undergoing cardiac catheterization for the assessment of angina have either minimal or no coronary artery obstruction at angiography [5] . For women younger than age 60 years of age, this proportion increases to almost 80% [6] . These patients present a challenge because it is often difficult to diagnose the etiology of and provide successful treatment for their chest pain.
• coronary flow reserve • endothelial dysfunction • ischemic heart disease • microvascular angina • microvascular
coronary dysfunction • nonobstructive coronary artery disease
●●Prognosis
While it was previously thought that these patients had no increase in cardiovascular risk, we now know that angina in patients with myocardial ischemia but without obstructive CAD does carry a poor prognosis [7] , as indicated in Figure 1. Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA, USA *Author for correspondence: [email protected] 1
10.2217/FCA.14.79 © 2015 Future Medicine Ltd
Future Cardiol. (2015) 11(2), 229–242
part of
ISSN 1479-6678
229
Review Titterington, Hung & Wenger
A
Survivor functions for men: age adjusted to 60 years
1.00
MACE-free survival
0.95 0.90 0.85 0.80 0.75
0
2
4 Time (years)
Asymptomatic Diffuse nonobstructive CAD 2VD 0 2359 1214 869 1475 1105 1783
Numbers at risk Asymptomatic Normal CA Diffuse nonobstructive CAD 1VD 2VD 3VD
2 2231 854 557 1072 806 1312
6
8
Normal coronary arteries 1VD 3VD 4 2101 597 362 783 583 984
6 1738 367 174 474 342 632
Survivor functions for women: age adjusted to 60 years
B
MACE-free survival
1.00 0.95 0.90 0.85 0.80 0.75
0
2
4
6
8
Time (years) Asymptomatic Diffuse nonobstructive CAD 2VD Numbers at risk Asymptomatic Normal CA Diffuse nonobstructive CAD 1VD 2VD 3VD
230
Future Cardiol. (2015) 11(2)
0 3346 2237 809 777 377 471
2 3213 1597 527 567 274 333
Normal coronary arteries 1VD 3VD 4 3044 1155 336 411 209 256
6 2600 721 187 252 143 161
future science group
Microvascular angina: an update on diagnosis & treatment
Review
Figure 1. Anginal symptoms in patients with normal appearing coronary arteries decrease survival in both men and women (see facing page). Degree of epicardial CA correlates with outcomes in (A) men and (B) women. Women with nonobstructive disease (green line) had worse outcomes than either asymptomatic women or women with normal CAs (maroon line). 1VD: 1-vessel disease; 2VD: 2-vessel disease; 3VD: 3-vessel disease; CA: Coronary artery; CAD: Coronary artery disease; MACE: Major adverse cardiac event. Reproduced with permission from [7]. For color figures, see online at: www.futuremedicine.com/doi/full/10.2217/FCA.14.79.
Similarly, in individuals without CAD undergoing noninvasive assessment, those with coronary microvascular dysfunction (defined by a noninvasive estimated coronary flow reserve [CFR] of
Microvascular angina: an update on diagnosis and treatment
Jane S Titterington1, Olivia Y Hung1 & Nanette K Wenger*,1
ABSTRACT Many patients with chest pain who are relieved to learn that they have no obstructive stenoses at diagnostic angiography are misclassified as having noncardiac chest pain. Only recently have we developed the conceptual framework and diagnostic tools to understand that ischemic heart disease is not exclusively caused by obstructive coronary artery disease, but often has its origin in the microcirculation. This article will focus on the diagnosis and treatment of microvascular angina as a cause of myocardial ischemia in patients with abnormal but ‘normal appearing’ coronary arteries. KEYWORDS
Background ●●Scope of the problem
Cardiovascular disease remains the leading cause of mortality in the USA, accounting for one of every three deaths. It is estimated that there are more than 1 million myocardial infarctions (MIs) each year [1] . Following an MI, nearly a third of patients develop systolic heart failure within 5 years [2] . Chronic stable angina, now characteristically referred to as stable ischemic heart disease (SIHD), affects 7.8 million people in the USA, and more than 50% of them (4.1 million) are women [1] . Approximately half a million new cases of angina occur annually [1] . In addition to the substantial morbidity and mortality, there is a huge economic cost associated with coronary artery disease (CAD). The WISE study was undertaken in order to evaluate symptomatic myocardial ischemia in women, with particular interest paid to those with angina but no epicardial coronary artery stenosis [3] . In this cohort, 62% of women with myocardial ischemia at noninvasive testing had nonobstructive coronary disease, and of those, 20% required hospitalization for chest pain within 5 years of initial angiography [4] . Women with nonobstructive CAD undergo angiography almost twice as frequently as women with single-vessel disease and have similar levels of disability and a higher angina burdens [4] . The lifetime medical costs for a woman in the WISE study with nonobstructive CAD is estimated to be US$770,000 [4] . Nearly half of patient undergoing cardiac catheterization for the assessment of angina have either minimal or no coronary artery obstruction at angiography [5] . For women younger than age 60 years of age, this proportion increases to almost 80% [6] . These patients present a challenge because it is often difficult to diagnose the etiology of and provide successful treatment for their chest pain.
• coronary flow reserve • endothelial dysfunction • ischemic heart disease • microvascular angina • microvascular
coronary dysfunction • nonobstructive coronary artery disease
●●Prognosis
While it was previously thought that these patients had no increase in cardiovascular risk, we now know that angina in patients with myocardial ischemia but without obstructive CAD does carry a poor prognosis [7] , as indicated in Figure 1. Emory University School of Medicine, Department of Medicine, Division of Cardiology, Atlanta, GA, USA *Author for correspondence: [email protected] 1
10.2217/FCA.14.79 © 2015 Future Medicine Ltd
Future Cardiol. (2015) 11(2), 229–242
part of
ISSN 1479-6678
229
Review Titterington, Hung & Wenger
A
Survivor functions for men: age adjusted to 60 years
1.00
MACE-free survival
0.95 0.90 0.85 0.80 0.75
0
2
4 Time (years)
Asymptomatic Diffuse nonobstructive CAD 2VD 0 2359 1214 869 1475 1105 1783
Numbers at risk Asymptomatic Normal CA Diffuse nonobstructive CAD 1VD 2VD 3VD
2 2231 854 557 1072 806 1312
6
8
Normal coronary arteries 1VD 3VD 4 2101 597 362 783 583 984
6 1738 367 174 474 342 632
Survivor functions for women: age adjusted to 60 years
B
MACE-free survival
1.00 0.95 0.90 0.85 0.80 0.75
0
2
4
6
8
Time (years) Asymptomatic Diffuse nonobstructive CAD 2VD Numbers at risk Asymptomatic Normal CA Diffuse nonobstructive CAD 1VD 2VD 3VD
230
Future Cardiol. (2015) 11(2)
0 3346 2237 809 777 377 471
2 3213 1597 527 567 274 333
Normal coronary arteries 1VD 3VD 4 3044 1155 336 411 209 256
6 2600 721 187 252 143 161
future science group
Microvascular angina: an update on diagnosis & treatment
Review
Figure 1. Anginal symptoms in patients with normal appearing coronary arteries decrease survival in both men and women (see facing page). Degree of epicardial CA correlates with outcomes in (A) men and (B) women. Women with nonobstructive disease (green line) had worse outcomes than either asymptomatic women or women with normal CAs (maroon line). 1VD: 1-vessel disease; 2VD: 2-vessel disease; 3VD: 3-vessel disease; CA: Coronary artery; CAD: Coronary artery disease; MACE: Major adverse cardiac event. Reproduced with permission from [7]. For color figures, see online at: www.futuremedicine.com/doi/full/10.2217/FCA.14.79.
Similarly, in individuals without CAD undergoing noninvasive assessment, those with coronary microvascular dysfunction (defined by a noninvasive estimated coronary flow reserve [CFR] of
