Imaging of heart disease in women: review and case presentation

CCTA allows the detection and assessment of coronary stenosis severity, with obstructive CAD being defined as a stenosis ≥ 70%, or ≥ 50% if ischemia is documented [41]. Despite an overall high diagnostic accuracy for the detection of stable CAD [40, 42], the sensitivity and specificity of CCTA is slightly lower in women than in men [43, 44], owing to the smaller diameter of coronary vessels in women as well as to their frequently higher heart rates resulting in motion artifacts and lower image quality [45]. Women with moderate or severe ischemia are more likely to have non-obstructive CAD (i.e., < 50% stenosis in all vessels) on CCTA than men [46], and they present angina symptoms for lower degrees of stenosis than men [47]. This could again be explained by the fact that women have smaller epicardial coronary arteries [48] and more often positive remodeling, which might become symptomatic at lower degrees of stenosis than in men [47], particularly in distal segments and side branches [44]. Additionally, the coronary diameter is a key parameter predicting image quality of CCTA examination, which is therefore more frequently lower in women than in men [49]. Nevertheless, CCTA results in lower use of additional testing and costs in women than in men, although at the expense of higher radiation exposure compared to functional testing [50].

Beyond detection of coronary stenosis, CCTA informs about plaque composition, which is of prognostic value regardless of the degree of stenosis. Indeed, evaluation of low-attenuation plaque volume (< 30 Hounsfield units) is a better predictor of future ACS than plaque calcification and stenosis severity [51]. This could be particularly interesting in women who usually exhibit lower plaque burden and calcifications than men [52], notwithstanding worse long-term outcomes [23]. Although women display less high-risk plaque features than men (low-attenuation plaques, positive remodeling, spotty calcifications, and napkin ring sign) [53], a study in 4415 patients with stable chest pain without known CAD showed that high-risk plaques found by CCTA were a stronger predictor of MACE in women than in men [54]. While calcified plaques are usually non-modifiable, the progression of non-calcified plaques can potentially be modified by preventive treatment such as statins [55]. Accordingly, the early detection of plaque progression with CCTA could result in an early initiation of treatment, which may improve patients’ outcomes [56]. Moreover, plaque regression under preventive treatment, as assessed by CCTA, is a promising imaging biomarker of treatment efficacy that may help tailor the therapeutic strategy [57].

Non-contrast cardiac computed tomography (CT), whose effective radiation dose amounts to < 1 mSv using contemporary scanners [58], can also provide valuable information about the calcified plaque burden in coronary arteries (Agatston coronary artery calcium score, CACS), a powerful predictor of subsequent MACE [59]. Although overall coronary calcium burden is lower in women than in men, CACS is a better predictor of MACE in the female population than in men, with a similar burden of calcified plaques being associated with a worse prognosis in women [60]. However, CACS does not rule out non-calcified plaques, stressing the importance of plaque composition analysis in women, in whom calcifications appear nearly 10 years later than in men [47]. Nevertheless, when matching the baseline plaque volume, the progression rate of plaque burden appears mediated mainly by calcified plaques in women and by non-calcified plaques in men [61]. Therefore, a careful evaluation of changes in plaque composition could help fine-tune the coronary risk stratification, especially in the female population [57]. Noteworthy, breast arterial calcifications are associated with subclinical CAD and their detection might improve risk stratification in asymptomatic women [62].

Additional novel CCTA tools have emerged lately, which could improve the detection of ischemia in women [63]. Indeed, it has been shown that adding CT perfusion to CCTA improves the specificity of ischemia detection compared to CCTA alone in women, but not in men [64]. CT-derived fractional flow reserve (FFR-CT) was shown to be higher in women than men regardless of stenosis degree, and women tend to have a lower likelihood of positive FFR-CT than men for a similar degree of coronary stenosis [65]. This highlights the need for sex-based thresholds and further studies exploring the incremental prognostic value of FFR-CT in women.

The use of CCTA remains limited in young women due to breast radiation exposure and in pregnant women, with estimated radiation of 0.5–7 mSv [66]. For a similar exposure from cardiac imaging, the risk of developing cancer is higher in women than in men, which could be related to relatively smaller body sizes in women [67]. Nevertheless, technological advances and refinements of the scanning protocol may allow a significant reduction of the effective breast tissue dose [68].

CMR is particularly interesting in women with suspected CAD because it is devoid of ionizing radiation exposure [69]. In women with stable CAD, CMR has a higher sensitivity than SPECT as demonstrated by the CE-MARC [70] and MR-IMPACT II studies [71]. Two CMR techniques are available to detect myocardial ischemia [72]: perfusion CMR using a vasodilator agent and requiring a gadolinium-based contrast agent to assess perfusion abnormalities, and dobutamine-stress CMR, which focuses on wall motion abnormalities and therefore does not require contrast agents. Noteworthy, the higher rate of side effects induced by vasodilator agents in women (such as headache, flushes, dizziness, chest pain, and nausea), in particular with adenosine [73], represents a limitation to their use. Interestingly, first-pass myocardial perfusion on vasodilator stress CMR can detect subendocardial ischemia even in the absence of significant coronary stenosis, a frequent presentation in women [30]. Although not yet implemented in clinical routine, quantification of myocardial blood flow (MBF) by rest/stress high-resolution perfusion CMR displays good accuracy to identify CMVD [74]. CMR’s high spatial resolution can also be useful in the follow-up of women with ACS undergoing revascularization, who present with smaller post-revascularization infarct size and myocardial salvage than men [75]. T1 and T2 mapping techniques and CMR-based measurement of extracellular volume (ECV) help to accurately assess the acute infarct size [76]. T1 mapping is highly sensitive to edema (such as in the acute phase of MI [77]), and fibrosis (such as in scarred myocardium following MI [78]). ECV measurement using mapping techniques also detects myocardial fibrosis with high sensitivity, complementing the data obtained from T1 mapping [79]. While late gadolinium enhancement (LGE) only highlights focal fibrosis [80], T1 and ECV mapping allow the detection of diffuse interstitial fibrosis, even in the early phases of the disease [81]. Similarly, T2 myocardial maps can be generated, which, if increased, indicate myocardial edema [82]. CMR mapping techniques simultaneously assess differential diagnoses of CAD in women such as myocarditis and TTC [83]. Indeed, early CMR imaging with T1 and ECV mapping techniques significantly improves the detection of acute phases of TTC compared to CMR without mapping, by evidencing myocardial edema in the affected area [83, 84].

Noteworthy, T1 and ECV values are higher in women than in men [85]. Additionally, T1 and ECV increase with age in males, but not in females [79], which could reflect the age-dependent increase of interstitial myocardial fibrosis in males observed in histopathological studies [86]. While these differences might be irrelevant in diseases inducing high levels of myocardial edema and/or fibrosis, they could become significant in diseases inducing mild changes, suggesting the need for sex-specific reference values for mapping parameters [79]. Another advantage of CMR in women as compared to SPECT is that CMR is devoid of breast attenuation artifacts [87]. Moreover, CMR is not associated with radiation exposure and is therefore encouraged over ionizing techniques (SPECT, PET) in premenopausal women with intermediate-to-high risk of CAD [88]. Nonetheless, a limitation of CMR in women is their higher rate of claustrophobia [89].

SPECT is the most common functional imaging technique for ischemia detection and risk stratification of women with stable CAD [90]. Despite overall high diagnostic accuracy in women [91], the detection of small areas of ischemia by SPECT-MPI can be limited in postmenopausal women who present with smaller left ventricular (LV) volumes, which in conjunction with the limited spatial resolution of SPECT induce image blurring [90]. In addition, SPECT-MPI cannot rule out CMVD [92] as it does not enable absolute quantification of MBF due to its low resolution. Another limitation of SPECT in women is breast tissue attenuation which can mimic perfusion defects, classically in the anterior wall [93]. Several techniques help to reduce attenuation artifacts including image acquisition in prone position, breast bandage, and CT-based attenuation correction [94]. Combining CT with SPECT also allows quantifying intrathoracic fat and CACS, which provide incremental prognostic value for MACE in women [95].

Radiation exposure represents a major drawback of SPECT-MPI in young women [96], with an estimated exposure of 2–8 mSv [66]. ^99mTc should therefore be favored over ²⁰¹Tl because of its lower radiation exposure [88]. Additionally, if stress imaging is normal, skipping rest acquisitions can decrease total radiation dose [97]. Highly sensitive cadmium-zinc-telluride-based detectors also allow the reduction of the amount of injected radiotracer and the associated radiation burden [98] while improving diagnostic accuracy in women with low-to-intermediate likelihood of CAD. Indeed, cadmium-zinc-telluride-based detectors reduce the percentage of artefactual perfusion defects, in particular those induced in the anterior wall by breast attenuation [99]. Similarly, PET-MPI is associated with a lower radiation exposure than SPECT [100]. Additionally, PET’s higher spatial resolution compared to SPECT reduces the rate of false negatives in women that are related to smaller LV size [90]. Moreover, PET-MPI (using either ¹³N-NH₃, ⁸²Rb, or ¹⁵O-H₂O) enables absolute quantification of myocardial perfusion, i.e., MBF and coronary flow reserve (CFR), which are key elements of CMVD [101]. Of note, MBF values at rest are higher and CFR values are lower in women than in men [102], and the predictive value of PET-derived MBF and CFR for MACE is lower in women than in men [103, 104]. On the other hand, a blunted heart rate response after pharmacological stress for ¹³N-NH₃-PET-MPI is a predictor of reduced CFR in women with suspected myocardial ischemia, but not in men [105]. More recently, ¹⁸F-flurpiridaz has emerged as a promising tracer for PET-MPI evaluation of MBF [106]. ¹⁸F-flurpiridaz-PET-MPI presents higher specificity than SPECT-MPI for the detection of CAD in women [107], which could be related to the preserved diagnostic performances of ¹⁸F-flurpiridaz-PET-MPI in patients with small ventricles [108]. Similar to SPECT-MPI, CT performed in combination with PET-MPI also helps correct breast attenuation artifacts [109].

With regard to plaque imaging, several studies have established the ability of vascular ¹⁸F-sodium fluoride PET (¹⁸F-NaF PET) to document the early stages of plaque microcalcification [110] and to predict the progression of coronary plaques [111]. Interestingly, the intensity of ¹⁸F-NaF uptake in atherosclerotic plaques of CVD-free patients is lower in women than in men [112], which seems consistent with the lower burden of calcified plaque in this population. Consequently, studies are needed to identify specific features of plaque progression other than calcification in the female population.

While echocardiography is the first-line exam to assess cardiac function [127], it may be technically limited in women because of a smaller acoustic window related to breast interference and higher prevalence of a concave-shaped chest wall in women [128]. CMR is therefore a valid alternative to echocardiography for imaging of cardiac volumes [125]. CMR is considered the reference standard to measure right and left chamber volumes and mass [125], to assess both systolic and diastolic functions, determine HF etiology, and look for complications in HFrEF [129] as well as in HFpEF [130]. Noteworthy, sex differences exist in the normal values of cardiac chambers, with lower left and right ventricular and atrial volumes as well as LV mass in women as compared to men, even after correcting for body surface area [131].

Based on local practices and availability of technologies, an alternative method is 2D-gated equilibrium radionuclide angiocardiography (ERNA), which robustly determines LVEF [132]. However, scintigraphy tends to underestimate the value of LVEF compared to CMR in both sexes [133].

CCTA also accurately assesses LVEF [134]. Despite this, concerns related to radiation exposure in women limit the use of CCTA and ERNA to patients with low echogenicity and contraindications to CMR [135, 136]. Also, due to the increasing use of prospective electrocardiogram (ECG) gating, which has resulted in lower radiation dose and better image quality [137], assessment of LV volumes by CCTA is no longer ubiquitously available.

The European Society of Cardiology (ESC) proposes a four-step algorithm to diagnose HFpEF [120]. First, women with dyspnea (especially on exertion) or orthopnea should undergo a pretest evaluation. This consists of screening for HFpEF risk factors such as obesity, metabolic syndrome/diabetes mellitus, physical inactivity, and arterial hypertension, recording ECG in search for atrial fibrillation (a highly predictive criteria for HFpEF) [138], and performing echocardiography or CMR showing LVEF ≥ 50%, non-dilated LV, concentric hypertrophy, and left atrial enlargement [120, 139] (Case 3). If the presentation is suggestive of HFpEF, an echocardiographic score is calculated based on a series of major and minor criteria which will not be detailed here [120]. In case the score does not allow ruling in or ruling out the diagnosis of HFpEF, a 3^rd step consists of considering diastolic dysfunction assessed by stress echocardiography, which alongside preserved LVEF is a cardinal feature of HFpEF [120, 139]. If the diagnosis still remains uncertain, invasive hemodynamic measurements using left and right heart catheterization are recommended with measurement of LV end-diastolic pressure and mean pulmonary capillary wedge pressure [120]. Once HFpEF is confirmed, the final step consists of an etiological workup. Given that CMVD is present in most patients with HFpEF [6], PET-MPI with calculation of CFR and MBF is recommended [120]. CMR detects most of the specific etiologies (ischemic cardiomyopathy, myocarditis, or restrictive cardiomyopathies), while CCTA can be most useful to evidence CAD [130]. In selected cases, bone scintigraphy and ¹²³I-meta-iodobenzylguanidine (¹²³I-MIBG) scintigraphy are useful to detect cardiac amyloidosis [140].

In case of HFrEF, the lower rate of ischemic origin in women stresses the importance of CMR with LGE and T1/T2 mapping techniques to establish alternative etiologies, such as dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), valvular heart disease (VHD) [141‐143], and arrhythmogenic right ventricular cardiomyopathy [144].

Although invasive imaging establishes the diagnosis of TTC in most cases, by ruling out coronary obstruction and showing the hallmark wall motion abnormality [145], multimodality imaging plays a key role in the diagnosis of TTC [146]. Echocardiography is the first-line exam, displaying the characteristic LV wall motion abnormality generally extending beyond a coronary territory. ICA is often required owing to the MI-like presentation of TTC, showing normal coronary arteries. Alternatively, CCTA can be performed in stable patients, ruling out CAD with high confidence. CMR with LGE and mapping techniques is a particularly comprehensive tool, revealing the typical kinetic abnormalities, myocardial edema (with increased T2-weighted signal and T1 mapping values), excluding differential diagnosis (particularly MINOCA and myocarditis), and detecting complications such as LV thrombi. Often overlooked, nuclear imaging tools can also establish the diagnosis, particularly in the subacute phase when wall motion has normalized thereby misleading other imaging tools (Case 4). In the subacute phase, nuclear MPI shows preserved perfusion, while ¹²³I-MIBG and ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) uptakes remain reduced despite normalization of ventricular kinetics [147]. Interestingly, 6-Fluoro-[18F]-l-3,4-dihydroxyphenylalanine (¹⁸F-DOPA) PET-based studies have documented an age-dependent increase in ¹⁸F-DOPA uptake in the LV apex of women, which was not present in men, indicating an enhanced sympathetic activity which could account for the higher susceptibility of postmenopausal women to TTC [18].

Two main challenges must be addressed when imaging pregnant women: (1) distinguishing pathological conditions from the physiological changes occurring during pregnancy; and (2) finding the optimal trade-off between radiation exposure and image quality [156].

During pregnancy, physiological adaptive cardiovascular changes occur [149]. These changes consist mainly of an increase in LV end-diastolic volume, LV mass, and cardiac output [157]. In addition, one out of four pregnant women shows an increase in LV trabeculation, which can mimic LV non-compaction cardiomyopathy [158]. Pregnancy is also associated with tachycardia [157], which can represent a technical limitation for ECG gating.

Radiation exposure during pregnancy increases the risk of breast cancer in the mother [159] and may induce miscarriage, malformation, or fetal cancer [160]. Consequently, pregnant women should preferentially undergo non-ionizing imaging, i.e., echocardiography or non-contrast-enhanced CMR [161]. It is nevertheless recommended to avoid magnetic resonance imaging > 1.5 Tesla due to concerns related to heating effect, especially during the 1^st trimester [69]. Additionally, fetal exposure to gadolinium at whatever stage of pregnancy increases the risk of stillbirth or neonatal death and should be limited to the only cases when the expected benefits clearly outweigh the risks [162].

If necessary, and in agreement with a fully informed patient, ionizing techniques should not be withheld from pregnant patients, together with or in replacement of non-ionizing techniques [162]. Indeed, although no threshold exists below which there would be no risk for the fetus (stochastic effect), the risk associated with fetal radiation < 100 milliGray is considered negligible, which is beyond the usual radiation doses of diagnostic imaging [163, 164]. The as low as reasonably achievable (ALARA) dose should always be the guiding principle (ideally < 50 milliGray [165]) while preserving image quality. This can be achieved by preferentially resorting to non-ionizing imaging, by optimizing CT parameters (preferential use of low voltage and of high pitch, careful selection of tube current, use of novel reconstruction algorithms, avoiding multiple phases imaging), and for nuclear imaging by opting for radiotracers with shorter half-life (^99mTc rather than ²⁰¹Tl [166]) and reducing the injected radiotracer activity [66, 167]. In case scintigraphy is performed, breastfeeding needs to be interrupted for > 12 h after the study due to the excretion of the radiotracer in the maternal milk [136].

Positioning during image acquisition is also important. Indeed, in the supine position, the gravid uterus can compress the inferior vena cava which may affect cardiac output; to prevent this, pregnant women should undergo imaging in the left lateral tilt position [168].

The incidence of PPCM is 1 per 1000–4000 live births in Western countries, but its incidence varies depending on predisposing factors including age > 30 years, black ethnicity, preeclampsia, hypertension, and multiparity [169]. Several pathophysiological hypotheses have been proposed to account for the development of PPCM (vascular, hormonal, and genetic) [170], but the exact underlying causes remain debated.

PPCM is defined as symptomatic LV systolic dysfunction with LVEF < 45%, developing either in the last month of pregnancy or in the 5 months following its end in women with no previously documented cardiac disease [171]. A simplified definition describes PPCM as an idiopathic HF developing towards the end of pregnancy or in the months following delivery [172]. This definition limits the risk of PPCM being under-diagnosed by too stringent timeframe cutoffs. Noteworthy, LVEF can be preserved or mildly impaired in early stages of PPCM [173]. Given the broadness of the diagnostic criteria, PPCM is in practice an exclusion diagnosis, retained after ruling out other cardiomyopathies and preexisting heart diseases, especially DCM that shares common clinical and genetic features with PPCM [174, 175]. The time of onset can help distinguishing both entities. DCM develops preferentially during late pregnancy, whereas PPCM usually occurs in the early weeks after delivery [176]. DCM must also be considered in case of familial history or preexisting LV dysfunction [177].

PPCM is usually reversible within 6 months after termination of pregnancy [178]. Factors associated with a lower rate of 12-month event-free survival or reduced LV functional recovery are LVEF < 30% at diagnosis, LV end-diastolic diameter > 60 mm, an involvement of the right ventricle (RV), and evidence of myocardial edema on CMR [179‐181].

The frontline imaging exam is echocardiography [181]. CMR also accurately measures cardiac volumes, and T2 imaging characterizes myocardial edema in postpartum women [182]. Moreover, CMR excludes differential diagnosis, such as myocarditis, TTC, and DCM, and reveals stigmas of previous cardiomyopathies [141, 154, 171, 181]. CMR can also identify LV thrombi, a classical complication of PPCM [183]. LGE can evidence myocardial scarring (in postpartum women when gadolinium can safely be used), which is associated with worse outcomes [184]. CMR screens for predictors of impaired prognosis such as RV involvement [180], and mid-myocardial local LGE [185] although the prognostic value of LGE in PPCM is debated [179, 181]. CMR can further be used to monitor functional recovery, thereby guiding the therapeutic strategy [154, 177] which consists of cautious use of conventional HF medications, taking into account the risk to the child during pregnancy or related to breastfeeding, as well as of bromocriptine [186].

Ionizing techniques are usually not needed to diagnose PPCM. However, they can be useful to exclude other causes of dyspnea and HF during pregnancy, mainly pulmonary embolism and CAD [181].

SCAD is an important cause of MI, especially in young and middle-aged women, and during pregnancy [187]. The reasons behind this sex dimorphism are not clear and could be linked to sex hormones as well as distinct susceptibility genes [187]. Although no sex chromosome-related gene has been identified, the overrepresentation of women in SCAD raises the question whether genes with estrogen response elements are implicated in the pathophysiology of this condition [187]. In pregnant women, the risk of SCAD is particularly high in the first week postpartum [188]. While the diagnosis is usually made by ICA, optical coherence tomography (OCT) and intravascular ultrasound are helpful in cases of uncertainty or to guide revascularization [187]. CCTA can show abrupt luminal interruption [187] and should be preferred in hemodynamically stable women, owing to the risk of aggravating the dissection by contrast injection in the coronary ostium during ICA [187]. CCTA typical findings include an intimo-medial flap, lumen narrowing, or even occlusion, caused by thrombosis or intramural hematoma [189].

Cancer therapy-related cardiac dysfunction (CTRCD) is the most common complication of cancer therapy (Case 7). CTRCD is defined as a drop in systolic LV function below the lower limit of normal (< 50% for the ESC, < 53% for the European Association of Cardiovascular Imaging) in the context of cancer treatment administration along with a > 10% decline from baseline value. Confirmation by repeating the study 2–3 weeks after initial diagnosis must be obtained [197]. An additional mandatory criterion is a reduction in global longitudinal strain (GLS) > 15% from baseline [197]. Guidelines do not distinguish male and female LVEF thresholds for the diagnosis of CTRCD. However, active breast cancer in chemotherapy-naïve patients is associated with increased strain amplitude and systolic strain rate [198]. This, in conjunction with the higher values of LVEF in postmenopausal women, highlights the need for specific cut-off values of LVEF and GLS in women to avoid missing early CTRCD signs.

While endomyocardial biopsy is the gold standard to diagnose CTRCD, noninvasive imaging is the most common diagnostic tool. Echocardiography is the frontline exam to measure LVEF and GLS [199]. Nevertheless, echocardiography can be limited in women because of a smaller acoustic window related to breast interference, especially in case of implants, a common situation after breast cancer [200]. Breast implants and reconstructive surgery also limit the quality of apical-view-based GLS measurement [201]. CMR provides a more accurate and reproducible measurement of ventricular volumes as well as of GLS than echocardiography [202] and is not affected by breast artifacts [87]. Additionally, ECV and native T1 mapping can detect signs of myocardial fibrosis in women with breast cancer exposed to anthracycline [203]. Interestingly, CMR-derived LVEF and strain are predictive of subsequent CTRCD in early stage HER2 + breast cancer receiving sequential anthracycline/trastuzumab [204]. A baseline percentage of normal myocardium ≥ 80% on CMR, defined as the percentage of LV myocardium with strain less than or equal to − 17%, helps identifying women with breast cancer at risk of CTRCD [205]. In those who do develop cardiotoxicity, normal myocardium ≥ 50% is predictive of recovery [205]. Although promising for the detection of subclinical cardiotoxicity, mapping techniques and ECV values tend to overlap between patients with and without CTRCD and need further evaluation [206]. Noteworthy, cancer itself and particularly breast cancer are associated with structural cardiac changes, such as smaller chamber sizes although without significantly affecting overall LVEF [198]. Additionally, breast cancer radiotherapy damages the coronary microvascular endothelium, hence promoting CMVD [207], a situation where high-resolution perfusion CMR could prove useful [74].

Alternatively, ERNA can be used to measure and monitor LVEF [208]. However, it should be noted that, in breast cancer patients receiving trastuzumab, ERNA-derived LVEF values are lower than those of CMR [209]. Nevertheless, the use of scintigraphy in women suffers limitations, related to breast tissue/implant attenuation, to the cumulative radiation exposure induced by serial follow-up, and to the fact that GLS cannot be derived from ERNA.

Anticancer treatment can lead to other myocardial diseases including CAD. The risk of CAD is particularly increased in women with left breast cancer undergoing radiotherapy, which can induce fibrous stenosis of the left anterior descending artery, and accelerates progression of existing plaques [210]. Similarly, atherosclerosis progression is accelerated in patients receiving alkylating-like agents, fluoropyrimidines, and platinum compounds (increasing the risk of arterial thrombosis and vasospasm) [211]. Interestingly, CT scan used to plan radiotherapy for breast cancer also enables measuring CACS, an independent predictor of ischemic heart disease [212]. Furthermore, a recent study has shown that ¹⁸F-FDG myocardial uptake pattern is predictive of altered myocardial perfusion. Using this information obtained from oncologic imaging exams might therefore be helpful in identifying patients at risk for future cardiovascular complications of anticancer therapy at an early stage [213].

VHD in cancer patients consist mainly of treatment-induced fibrosis/calcification leading to stenosis/regurgitation [214], and of cardiac masses obstructing the valves [215]. The risk of iatrogenic VHD is particularly marked in patients undergoing radiotherapy [215], and those receiving anthracycline [215, 216], hence in women treated for breast cancer. Echocardiography is the first-line modality to assess valve function [217]. CMR is the preferred alternative, particularly for regurgitant VHD [218]. CT is increasingly used in VHD, especially for the quantification of calcification and measurement of valve orifice area in aortic stenosis [219].