Diagnosis and management of concurrent cardiac disease: Coronary disease, dilated ascending aorta, and mitral and tricuspid valve disease

Prevalence and clinical impact

In randomized clinical trials, more than two-thirds of intermediate- and high-risk transcatheter aortic valve implantation (TAVI) candidates have coronary artery disease (CAD). ^,

• The impact of CAD on long-term outcomes after TAVI is unclear and the optimal treatment strategy remains controversial.

• Two recent meta-analyses showed discordant results regarding the influence of CAD on outcome in patients undergoing TAVI ( Table 5.1 ). Preliminary data from observational studies and a meta-analysis suggest that patients with complex CAD (high SYNTAX score >22) at baseline have worse outcome after TAVI compared with patients without or with less complex CAD (SYNTAX score <22).

  TABLE 5.1

  Meta-Analyses Evaluating the Impact of CAD in Patients Undergoing TAVI

  Data from D’Ascenzo F, Verardi R, Visconti M, et al. Independent impact of extent of coronary artery disease and percutaneous revascularisation on 30-day and 1-year mortality after TAVI: a meta-analysis of adjusted observational results. EuroIntervention. 2018;14:e1169-e1177; Sankaramangalam K, Banerjee K, Kandregula K, et al. Impact of coronary artery disease on 30-day and 1-year mortality in patients undergoing transcatheter aortic valve replacement: a meta-analysis. J Am Heart Assoc. 2017;6(10):e006092.

  First Author, Year	n	CAD (%)	History (%)	PCI (%)	Findings
  D’Ascenzo, 2018	8334 13 studies	47.9	Prior MI: 22.6 Prior PCI: 28.5 Prior CABG: 19	Before TAVI: 25 During TAVI: 1.7 Planned after TAVI: 0	CAD did not affect 30-day all-cause death both at univariable (OR 1.93 [0.84–4.28]) and at multivariable analysis (OR 1.57 [0.71–3.46])
  Sankaramangalam, 2017	8013 15 studies	48.7	Not specified	Before TAVI: 21.8 During TAVI: not specified Planned after TAVI: not specified	CAD did not affect 30-day all-cause death (OR 1.07 [0.82–1.40]). Significant increase in all-cause death at 1 year (OR 1.21 [1.07–1.36).

  CABG, Coronary artery bypass graft; CAD, coronary artery disease; MI, myocardial infarction; OR, odds ratio; PCI, percutaneous coronary intervention; TAVI, transcatheter aortic valve implantation.

• Large prospective studies are needed to address this relationship in detail.

Assessment and treatment of coronary artery disease

Coronary computed tomography angiography (CTA) is routinely performed in TAVI candidates for procedural planning. Coronary CTA has become a reliable method to exclude obstructive CAD in patients without aortic stenosis (AS) and in patients with low pretest probability and planned valvular heart surgery ( Fig. 5.1 ).

• Preprocedural coronary angiography is the gold standard to exclude CAD in TAVI candidates, although it is associated with additional risk for vascular complications and kidney injury.

• Preprocedural coronary CTA can also be used to exclude CAD before TAVI and avoid redundant invasive coronary angiography.

• Although coronary CTA has several limitations in TAVI candidates (older age, high prevalence of calcified CAD and atrial fibrillation, relative contraindication for administering β-blockers or nitrates), several studies showed that coronary CTA is useful to exclude CAD before TAVI (negative predictive value >90%) ( Table 5.2 ).

  TABLE 5.2

  Selection of Studies Comparing the Performance of Coronary CTA With Coronary Angiography for the Detection of CAD (>50% Stenosis)

  Data from Hamdan A, Wellnhofer E, Konen E, et al. Coronary CT angiography for the detection of coronary artery stenosis in patients referred for transcatheter aortic valve replacement. J Cardiovasc Comput Tomogr. 2015;9(1):31-41; Opolski MP, Kim W-K, Liebetrau C, et al. Diagnostic accuracy of computed tomography angiography for the detection of coronary artery disease in patients referred for transcatheter aortic valve implantation. Clin Res Cardiol. 2015;104(6):471-480; Matsumoto S, Yamada Y, Hashimoto M, et al. CT imaging before transcatheter aortic valve implantation (TAVI) using variable helical pitch scanning and its diagnostic performance for coronary artery disease. Eur Radiol. 2017;27(5):1963-1970.

  First Author, Year	n	History (%)	Findings (%)
  Hamdan, 2015	115	CAD: 52.1 Prior PCI: 29.5 Prior CABG: 20	Sensitivity: 95.9 Specificity: 72.7 PPV: 72.3 NPV: 96
  Opolski, 2015	475	CAD: not specified Prior PCI: 47.6 Prior CABG: 19.2	Sensitivity: 98.1 Specificity: 37.1 PPV: 67.3 NPV: 93.8
  Matsumoto, 2017	60	CAD: 24 Prior PCI: 10 Prior CABG: 3.3	Sensitivity: 91.7 Specificity: 58.3 PPV: 59.5 NPV: 91.3

  CABG, Coronary artery bypass graft; CAD, coronary artery disease; CTA, computed tomography angiography; NPV, negative predictive value; PCI, percutaneous coronary intervention; PPV, positive predictive value.

• On the other hand, when CTA cannot exclude CAD, invasive coronary angiography is indispensable (see Fig. 5.1 ).

Several small nonrandomized observational studies have shown that percutaneous coronary intervention (PCI) before TAVI is feasible and safe. Nevertheless, PCI before TAVI was not associated with beneficial 30-day and long-term survival compared with isolated TAVI ( Table 5.3 ).

• Current guidelines recommend treatment of CAD if high-grade stenoses (>70%) in proximal segments are observed. However, evidence for this recommendation is lacking (class C recommendation) and the management of concomitant CAD remains a matter of debate.

• Several observational studies and meta-analyses analyzed the impact of complete revascularization on TAVI outcome.

• The residual SYNTAX score (an objective tool to assess extension and complexity of residual CAD after PCI) was used to define completeness of revascularization.

• In most of the studies a high residual SYNTAX score (equivalent to incomplete revascularization) was associated with an increased risk of mortality compared with patients with a low residual SYNTAX score (equivalent to complete revascularization).

• However, the ACTIVATION trial (a randomized controlled trial of PCI versus no PCI before TAVI) demonstrated no difference in the primary endpoint of death or rehospitalization at 1 year between pre-TAVI PCI and no PCI in the presence of nonextensive CAD and in the absence of angina.

• These findings need to be confirmed in large prospective randomized trials.

There is clear evidence that, in the absence of aortic stenosis, visual estimation for predicting the hemodynamic significance of a coronary stenosis based on angiography alone is limited.

• Functional assessment of CAD using fractional flow reserve (FFR) or nonhyperemic pressure ratios (e.g., instantaneous wave-free ratio [iFR] or resting full cycle ratio [RFR]) is the gold standard in patients with intermediate coronary lesions and no aortic stenosis.

• Preliminary data have shown that FFR and iFR in TAVI candidates appears overall to be safe and feasible; however, 1 in 10 patients do experience hemodynamic instability with systemic adenosine.

• Furthermore, studies have shown that FFR can underestimate lesion severity in the context of aortic stenosis with greater variability after TAVI compared with iFR.

• The iFR cutoff value for intervention is different in aortic stenosis. Therefore a hybrid approach using both iFR and FFR is recommended if physiologic assessment is deemed necessary.

• Functional assessment of CAD in patients with aortic stenosis before TAVI can avoid unnecessary stenting.

• Therefore, while we await prospective clinical trial data, the use of functional assessment to further evaluate coronary stenosis in TAVI candidates may help guide decision making ( Fig. 5.2 ).

  

Limited data exist regarding the optimal timing of revascularization relative to the TAVI procedure. Revascularization can be performed before TAVI as a staged procedure or concomitant during the same procedure. Both options are feasible and safe.

The decision on the timing of revascularization should be made based on individual anatomic and clinical characteristics.

• Decision to perform PCI before TAVI should also take into consideration bleeding risk and antithrombotic strategy.

• The aforementioned ACTIVATION trial showed significant increased bleeding in the PCI group driven by increased frequency of dual antiplatelet therapy.

• Staged PCI should be considered in patients with complex CAD (to focus on the treatment of difficult coronary lesions) and/or severe renal impairment (to limit the cumulative dose of contrast), whereas a simultaneous approach of PCI and TAVI can be considered in patients with a low procedural complexity and preserved renal function to avoid an additional invasive procedure.

• There is limited evidence for post-TAVI PCI; however, patients with intermediate lesions may, at a later stage, develop angina and should be treated as per guideline recommendations for stable coronary artery disease.