Heart failure (HF) affects more than 5.1 million Americans and is responsible for more than 1 million hospitalizations each year.¹ Current projections reveal that the prevalence of HF will increase by 46% by 2030, increasing the total HF population to more than 8 million. By the age of 40, the lifetime risk of developing HF will be 1 in 5.² Coronary artery disease (CAD) accounts for about two-thirds of the cases of HF with reduced ejection fraction (EF), and identifying ischemic disease as the primary etiology not only has treatment and long-term prognostic implications but is also associated with worse long-term outcomes.³ The Framingham Heart Study data suggest that hypertension and valvular heart disease are no longer the most common etiologies for HF. Rather, improvements made in treating acute coronary syndromes have led to a dramatic increase in the odds that any newly diagnosed cardiomyopathy will now be secondary to ischemic heart disease.⁴ Multi-ethnic studies have found that African Americans have the highest proportion of incident HF not preceded by clinical myocardial infarction (75%).⁵ In the patient with newly diagnosed HF with reduced EF with cardiovascular risk factors, ongoing typical angina is not enough to diagnose an ischemic etiology for the underlying HF. There is a paucity of data on whether patients with an unknown etiology of HF should undergo routine coronary angiography to rule out CAD. Patients with severe CAD may not report angina, especially among diabetic or female patients, and many cardiologists recommend screening coronary angiography in most, if not all, newly diagnosed patients with reduced EF. Currently, the American College of Cardiology/American Heart Association guidelines give a Class IIa indication with Level of Evidence C (which is an expert opinion and denotes a lack of significant clinical data) for performing angiography in all newly diagnosed patients.⁶ For those patient with symptoms of angina or a history of myocardial infarction, the American College of Cardiology/American Heart Association give a Class I indication with Level of Evidence B for performing coronary angiography.

The STICH (Surgical Treatment for Ischemic Heart Failure) trial compared patients with left ventricular systolic dysfunction and ischemic disease and randomized them to coronary artery bypass grafting plus medical therapy or medical therapy alone. The investigators found that patients who also underwent surgical revascularization had a reduction in death by pump failure and sudden cardiac death when compared with standard medical therapy alone. These benefits were primarily seen after 2 years.⁷

The identification of CAD has additional implications beyond simple revascularization. Patients with ischemic HF may additionally benefit from secondary preventive measures such as daily aspirin and statin drug therapy. Even though angina is more likely to occur in patients with CAD, it is frequently seen in the absence of CAD as well. This is especially applicable to the chronic HF patient at the time of an acute presentation. They often experience angina-like chest pain due to elevated left ventricular end-diastolic pressure with resultant subendocardial ischemia but without epicardial coronary obstruction. Myocardial perfusion imaging is often used in this clinical scenario to identify viable myocardium and those patients who could benefit from coronary revascularization.³

In the last several years, there have been two studies that have looked at the prevalence of angiographically significant CAD in patients with HF with reduced EF. In a retrospective study by Silva et al., they found that out of a total of 168 patients being followed in a HF clinic, CAD was the etiology of HF with reduced EF in one-third of the patients without angina and no prior cardiac events.⁸ Even without any cardiac risk factors, more than 10% of both men and women had significant CAD. Doukky et al. formed a derivation cohort from 124 consecutive patients who had undergone coronary angiography with a primary diagnosis of systolic HF of unclear etiology (EF <50%). Using multivariate logistic regression analysis, they derived a prediction rule for severe CAD (≥50% diameter stenosis in the left main, 3-vessel CAD, and 2-vessel CAD involving the proximal left anterior descending artery). The diagnostic performance of their defined prediction rule was then prospectively validated in a separate cohort of 143 patients recruited from 2 institutions. In the derivation cohort, 27% had CAD, including 15% with severe CAD.⁹ In this validation cohort (compiled from two academic centers), significant CAD was present in 36% of patients with HF with reduced EF who were selected for coronary angiography, including 17% with CAD severe enough to warrant surgical revascularization. They found that the presence of two or more nondiabetic risk factors (age ≥55 for men, age ≥65 for women, hypertension, tobacco use, and dyslipidemia) was a strong predictor of CAD. The presence of Q waves or left bundle branch block on electrocardiogram was independently predictive of severe CAD. Having one of these three predictors (diabetes, two or more nondiabetic risk factors, or Q waves or left bundle branch block on electrocardiogram) was associated with 97% sensitivity and 32% specificity for significant CAD and 100% sensitivity and 28% specificity for severe coronary artery bypass grafting anatomy. This study was limited in that it was subject to selection bias and had a small number of participants, but for those with an intermediate likelihood of CAD by prediction score, they speculated that noninvasive testing could have been used as an adjunct to enhance specificity. Future larger prospective studies are warranted to demonstrate utility of this clinical tool.

Ischemic HF remains the majority etiology of newly diagnosed cardiomyopathy. Although current guidelines give a Class IIa indication for performing routine angiography for all patients with newly diagnosed HF who lack symptoms of chest pain, we recommend it may be prudent to evaluate all patients, but especially those with American Heart Association Stage D HF being evaluated for mechanical circulatory device therapies. Implantation of mechanical circulatory support is increasingly used for the treatment of end-stage HF, and despite technological advancements and use of the continuous flow left ventricular assist devices (LVAD), right ventricular failure (RVF) still complicates 20% of LVAD implantation cases and contributes to significant postoperative morbidity and mortality, most notably in those patients with nonischemic cardiomyopathy where both ventricles are often equally impaired.^10,11 Many different risk scoring systems have been proposed for predicting RVF post-LVAD implantation, although none has been prospectively studied. Most commonly, the scoring systems combine clinical, hemodynamic, and laboratory parameters. For example, the Fitzpatrick and the Michigan right ventricular (RV) score include some of the following: the bilirubin and/or aspartate aminotransferase (as a marker of liver dysfunction), systemic blood pressure (hypotension as a marker of morbidity), serum creatinine (marker of renal dysfunction), cardiac index or RV stroke work index, or the need for vasopressors.¹¹ Interestingly, none of the various scoring systems discuss the need for a pre-operative assessment or re-assessment for CAD, specifically obstructive disease of the right coronary artery, as a possible predictor for postimplant RVF. Obviously, an acute total occlusion or even significant ischemia of the right coronary artery would lead to RV dysfunction in the peri-implantation period and could prove catastrophic. Total RVF would lead to inadequate anterograde flow from the RV to the LVAD or any forward output it could still provide, maybe at the expense of significantly elevated filling pressures. This is similar to the intraoperative RV injury that can occur during cardiopulmonary bypass such as poor cardioprotection, right coronary air embolus, or pulmonary hypertension associated with cardiopulmonary bypass.¹²

Data are currently lacking as to when patients already diagnosed with a cardiomyopathy, either ischemic or nonischemic, should have another assessment of their coronary anatomy to determine if there has been progression or development of obstructive atherosclerosis. A pragmatic approach would be that any patient presenting with a significant drop in left ventricular EF or with symptoms of angina would get an evaluation with coronary angiography unless contraindicated. Even in this scenario, there are no definitive guidelines or recommendations, and the individual practitioner must determine what percentage change in EF denotes a significant drop. Given inter- and intra-observer variability in determining left ventricular function by echocardiography, a drop by 10-15% or more likely warrants further work-up.

Ischemic heart disease today is the number one reason for systolic HF. Therefore, it is reasonable that all patients labeled as having a nonischemic cardiomyopathy who were admitted with an acute HF exacerbation and found to have a new drop in EF should have an assessment for underlying CAD prior to hospital discharge. Although clinical tools have been proposed like the one by Doukky et al. to predict which chest pain-free patients would have a high probability of having CAD as an etiology for HF,⁹ we believe that until well-validated models are available to risk stratify patients, the overwhelming prevalence of CAD as an etiology for HF is high enough to warrant a more aggressive approach. The early detection and treatment of CAD may help delay cardiomyocyte death, adverse ventricular remodeling, and the onset of Stage D HF. In addition, diagnosing a patient with heart disease changes long-term treatment goals because optimal medical therapy then includes high-dose statins and aspirin in addition to the standard goal-directed HF medications.

References

1. Go AS, Mozaffarian D, Roger VL, et al. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation 2014;129:399-410.
2. Heidenreich PA, Albert NM, Allen LA, et al. Forecasting the impact of heart failure in the United States: a policy statement from the American Heart Association. Circ Heart Fail 2013;6:606-19.
3. Gheorghiade M, Sopko G, De Luca L, et al. Navigating the crossroads of coronary artery disease and heart failure. Circulation 2006;114:1202-13.
4. Lloyd-Jones DM, Larson MG, Leip EP, et al. Lifetime risk for developing congestive heart failure: the Framingham Heart Study. Circulation 2002;106:3068-72.
5. Bahrami H, Kronmal R, Bluemke DA, et al. Differences in the incidence of congestive heart failure by ethnicity: the multi-ethnic study of atherosclerosis. Arch Intern Med 2008;168:2138-45.
6. Hunt, SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll Cardiol 2009;53: e1-e90.
7. Carson P, Wertheimer J, Miller A, et al. The STICH trial (Surgical Treatment for Ischemic Heart Failure): mode-of-death results. JACC Heart Fail 2013;1:400-8.
8. Silva F, Borges T, Ribeiro A, et al. Heart failure with reduced ejection fraction: Should we submit patients without angina to coronary angiography? Int J Cardiol 2015;190:131-2.
9. Doukky R, Shih MJ, Rahaby M, et al. A simple validated clinical tool to predict the absence of coronary artery disease in patients with systolic heart failure of unclear etiology. Am J Cardiol 2013;112:1165-70.
10. Kormos RL, Teuteberg JJ, Pagani FD, et al. Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes. J Thorac Cardiovasc Surg 2010;139:1316-24.
11. Fitzpatrick JR 3rd, Frederick JR, Hsu VM, et al. Risk score derived from pre-operative data analysis predicts the need for biventricular mechanical circulatory support. J Heart Lung Transplant 2008;27:1286-92.
12. Chen JM, Levin HR, Rose EA, et al. Experience with right ventricular assist devices for perioperative right-sided circulatory failure. Ann Thorac Surg 1996;61:305-10.

Keywords: Acute Coronary Syndrome, Angina Pectoris, Aspartate Aminotransferases, Atherosclerosis, Bundle-Branch Block, Cardiomyopathies, Cardiopulmonary Bypass, Constriction, Pathologic, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Death, Sudden, Cardiac, Echocardiography, Electrocardiography, Embolism, Heart Failure, Heart Valve Diseases, Heart-Assist Devices, Myocardial Infarction, Myocardial Perfusion Imaging, Myocytes, Cardiac, Risk Factors, Stroke, Ventricular Function, Left, Ventricular Remodeling

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