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For decades Coronary Angiography (CA) has represented the gold standard for the diagnosis and management of coronary artery disease (CAD). Today, invasive cardiologists can overcome the limits of such a binary approach, based on the definition of obstructive or nonobstructive stenosis, and go deeply into the characterization of individual coronary atherosclerosis. Indeed, several auxiliary imaging techniques allow a more accurate definition of global coronary atherosclerotic burden and single plaque composition. These techniques, integrating CA “luminal” data, assure a better definition of CAD pathophysiology and detection of vulnerable lesions, resulting in improved stratification of individual cardiovascular risk. Furthermore, this hybrid invasive approach can be used to monitor the response to specific intensive pharmacotherapy aiming to reduce atherosclerosis progression. This chapter reviews the main characteristics of imaging modalities currently available to invasive cardiologists, summarizes clinical evidence supporting their use, and illustrates possible future medical implications.

Objective: Global longitudinal strain (GLS) predicts major adverse events in ST-segment elevation myocardial infarction (STEMI) and aortic stenosis (AS). Different cut-off values and different end-points have been proposed for prognostic stratification. We aimed to verify whether a single GLS cut-off value can be used to identify increased risk of all-cause death in STEMI and AS.Patients and methods: One-hundred- seventeen successfully treated first STEMI (age 63.8 +/- 12.5 yrs, 70% men) and 64 AS (age 80.3 +/- 6.9 yrs, 44% men) patients, undergoing echocardiography before discharge and before AS treatment, respectively, were retrospectively analyzed. GLS was analyzed, together with pulmonary artery systolic pressure (PASP), Killip class and Genereux stage. End-point was all-cause death at 6-month follow-up.Results: All-cause death occurred in 4 (3.4%) STEMI and 5 (7.8%) AS patients (p=ns). AS patients who died had GLS similar to died STEMI patients (9.7 +/- 2.1 vs. 11.3 +/- 1.7, p=ns). GLS cut-off <= 12% predicted death with 89% sensitivity and 70% specificity (AUC 0.84, p=0.001): STEMI and AS patients with GLS <= 12% had worse survival than STEMI and AS patients with GLS >12% (log-rank p=0.001). At multivariate Cox regression analysis, lower GLS values independently predicted death (HR 0.667, 95% CI 0.451-0.986, p=0.042), and the prediction model was improved when GLS was added to old age, significant comorbidities, PASP and Killip/Genereux stage (chi 2 6.691 vs. 1.364, p=0.010).Conclusions: Died patients with STEMI and AS show similar values of GLS. A unique cut-off value of GLS can reliably be used to stratify the risk of all-cause death at 6-month follow-up in both two clinical settings.

Background: Different studies suggest that fulvestrant 500 mg every 28 days (HD-FUL) could be an active treatment in HR+ advanced breast cancer (ABC) patients even treated with aromatase inhibitors in the adjuvant setting. The aim of this analysis is to describe the outcome of ABC patients treated with HD-FUL as first-line treatment in terms of median duration of treatment and the overall response rate in a real-world setting. Methods: For the purpose of the present analysis, we considered two data sets of HR+ ABC patients collected in Italy between 2012 and 2015 (EVA and GIM-13 AMBRA studies). Results: Eighty-one and 91 patients have been identified from the two data sets. The median age was 63 years (range 35-82) for the EVA and 57.8 years (range 35.0-82.3) for the AMBRA patients. ORRs were 23.5 and 24.3% in the whole population, 26.9% in the patients with bone only, and 21.8 and 21.4% in those with visceral metastases. The median duration of HD-FUL was 11.6 months (range 1-48) and 12.4 months (range 2.9-70.0) in the two data sets, respectively. Conclusion: These data suggest that HD-FUL should still continue to play a significant role as first-line therapy in HR+ ABC patients.

Aims: There are limited data about the intraprocedural haemodynamic study performed immediately before and after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). We aimed to evaluate the acute haemodynamic impact of TAVI in patients with severe AS and to investigate invasive and non-invasive parameters predicting all-cause mortality. Methods and results: A total of 245 consecutive AS patients (43% male, mean age 80.3 ± 7.3 years) undergoing TAVI were enrolled. Intraprocedural left heart catheterization (LHC) and echocardiogram before and after TAVI were performed. The clinical endpoint was the death for any cause. LHC after TAVI revealed significant changes in aortic and left ventricular (LV) pressures, including indexes of intrinsic myocardial contractility and diastolic function such as positive dP/dT (1128.9 ± 398.7 vs. 806.3 ± 247.2 mmHg/s, P ˂ 0.001) and negative dP/dT (1310.7 ± 431.1 vs. 1075.1 ± 440.8 mmHg/s, P ˂ 0.001). Post-TAVI echo showed a significant reduction in LV end-diastolic (P = 0.036) and end-systolic (P ˂ 0.001) diameters, improvement in LV ejection fraction (from 55 ± 12% to 57.2 ± 10.5%, P ˂ 0.001), and pulmonary artery systolic pressure (42.1 ± 14.2 vs. 33.1 ± 10.7 mmHg, P < 0.001). After a mean follow-up time interval of 24 months, 47 patients died. Post-TAVI significant aortic regurgitation at echocardiography was the only independent predictor of mortality (hazard ratio 5.592, confidence interval 1.932–16.184, P = 0.002). Conclusions: Left heart catheterization performed immediately before and after prosthesis release offers a unique insight in the assessment of LV adaptation to severe AS and the impact of TAVI on LV, catching changes in indexes of intrinsic contractility and myocardial relaxation. Aortic regurg

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2–4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5–5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events. Graphical abstract: [Figure not available: see fulltext.]

Objective: The objective of this study is to compare hemodynamic and echocardiographic findings between valve-in-valve (VIV) and native-valve (NV) patients submitted to transcatheter aortic valve implantation (TAVI) due to pure aortic regurgitation (AR). Background: Patients with severe AR are surgically treated with variable postinterventional left-ventricular (LV) “reverse remodeling.” TAVI might be considered in selected AR patients. Methods: Twenty-eight patients with pure severe AR caused by either degenerated bioprosthesis or NV disease were successfully treated by TAVI at our institution. LV catheterization before and after TAVI and echocardiography before, after (24–72 h), and at follow-up (3–12 months) were performed. Results: Baseline clinical, hemodynamic, and echocardiographic characteristics were comparable between the two study groups, except for a younger age, higher proto-diastolic LV pressure, and higher LV end-systolic diameter in the NV group. At catheterization, an immediate hemodynamic impact of TAVI in both groups was noticed, with a trend toward better postprocedural residual regurgitation index and significantly lower LV dP/dT values (666.0 ± 177.9 vs. 883.5 ± 259.7 mmHg/s, p = 0.04) in VIV. At echocardiography, both NV and VIV patients showed favorable (early and sustained) post-TAVI echocardiographically detectable reverse remodeling. VIV patients also showed more pronounced early reduction in indexed LV end-diastolic volume (68.1 ± 27.4 vs. 86.5 ± 28.9 ml/m2 in VIV, p < 0.001 and 81.0 ± 29.0 vs. 95.2 ± 37.8 ml/m2 in NV, p = 0.043). Conclusions: Successful TAVI induces a striking hemodynamic impact with major structural (reverse remodeling) consequences in patients with pure AR caused by both bioprosthesis degeneration or NV disease. In the immediate postrelease phase, VIV patients might exhibit a more pronounced early LV contractile and structural benefit.

Few data are available on the prevalence of right ventricle (RV) systolic dysfunction, assessed including RV strain, and RV to pulmonary artery (PA) coupling in patients with aortic stenosis (AS) submitted to TAVI and the early effect of the procedure. We performed standard and speckle tracking echocardiography in 80 patients with severe AS the day before TAVI and within 48 h after TAVI. In all patients we measured TAPSE/PASP (cut-off for RV-PA uncoupling 0.31) and in 60/80 we were able to analyze RV global longitudinal strain (RV-GLS) and RV free wall strain (RV-FWS). RVFAC and TAPSE were impaired in 8.3% while RV-GLS and RV-FWS in 45% and 33.3% respectively before TAVI. TAPSE/PASP < 0.31 was documented in 7/80 patients (8.7%) before TAVI. These subjects differed from patients with TAPSE/PASP ≥ 0.31 for: enlarged left ventricular (LV) end-diastolic and end-systolic volumes (p < 0.001), worst LV ejection fraction (p < 0.001) and RVFAC (p < 0.001), worst RV-GLS and RV-FWS (p = 0.01 and p = 0.03) and bigger right atrium (RA) area (p < 0.001). After TAVI, RV systolic function did not improve while PASP significantly decreased (p = 0.005) driving the improvement of TAPSE/PASP (p = 0.01). Patients with TAPSE/PASP improvement (51%) differed from the others for worst pre-TAVI diastolic function (E/eʹ p = 0.045), RVFAC (p = 0.042), RV-GLS (p = 0.049) and RA area (p = 0.02). RV-GLS unveils RV systolic dysfunction in as much as 45% of patients with AS vs only 8.3% revealed by conventional echocardiography. RV systolic function does not significantly improve early after TAVI while RV-PA coupling does. Patients with lower TAPSE/PASP at baseline have worst LV and RV systolic function as well as larger RA. Patients who improve TAPSE/PASP after TAVI are those with worst diastolic function, RV systolic function and larger RA at baseline.

Severe calcific aortic stenosis (AS) and coronary artery disease (CAD) have common risk factors and are frequently encountered in the same patient in clinical practice. CAD has been reported in ≥ 50% of AS patients undergoing both surgical treatment and transcatheter aortic valve implantation (TAVI). In the last two decades, TAVI has been established as a less invasive alternative to surgery. Recently, more and more young and low surgical risk patients undergo TAVI. Despite the high prevalence of CAD in patients treated with TAVI, the management strategy of concomitant CAD in these patients remains an area of considerable uncertainty. This review provides an updated overview of the current knowledge about this topic and offers points for reflection about the best approach to use.

Valvular heart diseases (VHD) are common in the elderly population and several therapeutic options are available to treat them. When selecting the management strategy for VHD patients, to evaluate the operatory risk, using special scores like STS score, EuroSCORE II and other more specific ones is pivotal. However, the risk scores do not consider some aspects, such as the clinical needs of the single patients, the management of local resources and the expertise of the center. The Heart Team, combining the experience of various specialists, can optimize the decision-making process through a better evaluation of the risk/benefit ratio of the therapeutic choices. The multidisciplinary discussion of the most complex cases is recommended by the international guidelines for the management of VHD and it is part of the clinical practice of many centers. So far, both trials and large clinical studies supporting such multidisciplinary management are lacking. Despite these important limitations, the Heart Team can be actually regarded as a promising tool to locally promote best practices for the treatment of VHD patients.

In humans, the most common anatomic variation of the left main (LM) stem is represented by its distal division in 3 branches (LM trifurcation) instead of 2. LM trifurcation disease accounts for ≈10% to 15% of all LM diseases and is often managed by cardiac surgery. Over the last decades, due to the improvement of interventional material and techniques, percutaneous coronary intervention started gaining acceptance to treat patients with LM disease including those with trifurcated anatomy. Yet, LM trifurcation stenosis with its intrinsic anatomic complexity (3 branches, at least 4 angles, wide variability in branch size and disease) is recognized as a challenging lesion subset for percutaneous coronary intervention. In this review, we summarize available data about LM trifurcation anatomy, its influence on percutaneous coronary intervention feasibility, and the evidence collected regarding the different technical options (including trissing balloon inflation).

Background: Coronavirus disease 2019 (COVID-19) has caused an unprecedented change in the apparent epidemiology of acute coronary syndromes (ACS). However, the interplay between this disease, changes in pollution, climate, and aversion to activation of emergency medical services represents a challenging conundrum. We aimed at appraising the impact of COVID-19, weather, and environment features on the occurrence of ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in a large Italian region and metropolitan area. Methods and results: Italy was hit early on by COVID-19, such that state of emergency was declared on January 31, 2020, and national lockdown implemented on March 9, 2020, mainly because the accrual of cases in Northern Italy. In order to appraise the independent contribution on changes in STEMI and NSTEMI daily rates of COVID-19, climate and pollution, we collected data on these clinical events from tertiary care cardiovascular centers in the Lazio region and Rome metropolitan area. Multilevel Poisson modeling was used to appraise unadjusted and adjusted effect estimates for the daily incidence of STEMI and NSTEMI cases. The sample included 1448 STEMI and 2040 NSTEMI, with a total of 2882 PCI spanning 6 months. Significant reductions in STEMI and NSTEMI were evident already in early February 2020 (all p<0.05), concomitantly with COVID-19 spread and institution of national countermeasures. Changes in STEMI and NSTEMI were inversely associated with daily COVID-19 tests, cases, and/or death (p<0.05). In addition, STEMI and NSTEMI incidences were associated with daily NO2, PM10, and O3 concentrations, as well as temperature (p<0.05). Multi-stage and multiply adjusted models highlighted that reductions in STEMI were significantly associated with COVID-19 data (p<0.001), whereas changes in NSTEMI were significantly associated with both NO2 and COVID-19 data (both p<0.001). Conclusions: Reductions in STEMI

Coronary artery obstruction (CAO) during transcatheter-aortic-valve replacement (TAVR) represents a main concern for TAVR safety in patients with low coronary take-off. To date, “snorkel” (also called chimney) technique, consisting of stent implantation from the coronary ostium to the aorta within the space between the valve frame and the aortic wall, is the most adopted strategy to prevent CAO. This technique is associated with the creation of complex valve/stent configuration that can hinder repeat coronary interventions. Due to this concern, we set up an original sequence for coronary protection aiming to ensure a more physiological TAVR frame/stent configuration. According to this technique, TAVR prosthesis is released with a “protection” system consisting of guiding catheter (GC), wire and stent inside the coronary artery with high CAO risk. In the case of CAO occurrence, the stent is released according to the snorkel technique. In the absence of complete CAO, a new GC is advanced inside the implanted TAVR prosthesis and the stent is deployed from the coronary artery up to the prosthesis. We herein report two cases of very high CAO risk where this technique was successfully used during last-generation self-expandable prostheses implantation (in a native aortic valve and in one prosthetic aortic valve). In conclusion, this “orthotopic snorkel-stenting in TAVR” (OST) technique represents a novel option for treating impeding CAO during TAVR. As compared with the “classic” snorkel technique, it allows avoiding stent implantation in some patients (who do not experience CAO) and may provide a more predictable and physiologic TAVR prosthesis/stent configuration in the case of stent implantation need.

Background PCI in CBL is common and technically demanding. Whether such patients have adverse outcome during the follow-up after successful PCI is unclear. We aim to compare the clinical outcome after percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation of coronary bifurcation lesions (CBL) and non-CBL. Methods We performed a systematic literature search to identify studies reporting the clinical outcome of patients undergoing PCI in CBL or not. Patients with left main disease constituted a predefined subgroup. Primary study end-point was major adverse cardiac events (MACE). Results Fifteen publications on 23 891 patients with coronary artery disease treated by DES in CBL or not were identified. Median follow-up length was 24 months (range: 12-60). MACE at the longest available follow-up were significantly higher in CBL as compared with non-CBL (19.0 vs. 12.1%, P < 0.001). Similar results were obtained in the subanalysis restricted to second-generation DES studies. The MACE rate was higher early, then decreased during the follow-up being, however, appreciable at all timings up to 36 months. In the left main (LM) subanalysis (four studies, 3210 patients), patients underwent DES implantation in distal LM, as compared with nondistal LM, had increased the MACE rate during the follow-up (27.4 vs. 17.4%, P < 0.001), which was driven by higher target vessel revascularization. Conclusions In the contemporary DES era, CBL represent a subset of lesions associated with increased rate of MACE after PCI. This data prompt for studies aimed at improving the clinical outcomes of patients with CAD.

AIMS: The goal of the present post hoc analysis of the CLIMA registry was to establish the relationship between calcified nodules (CNs) with (CND) or without (CNWD) disruption of the superficial intimal fibrous layer and one-year occurrence of target lesion myocardial infarction (MI) and/or cardiac death. METHODS AND RESULTS: CND and CNWD were identified based on the presence or absence of superficial irregularities indicative of disruption of the intimal fibrous layer, with possible overlying local thrombus. In total, 222 CNs were found in the 1,776 non-culprit LAD plaques. CND had larger maximum calcific arc and smaller lumen area. Cardiac death and MI occurred in 20% of patients in the CND group versus 2.7% in the CNWD group and 3.3% in the group without CN (p<0.001). This figure was mainly due to the 13.3% incidence of cardiac death in the CND group versus 2.0% in the CNWD group and versus 2.2% in the group without CN (p<0.001). The presence of CND was confirmed as an independent predictor of events (HR 6.58, 95% CI: 2.7-15.8, p<0.001). CONCLUSIONS: The presence of CND was associated with a high one-year incidence of cardiac death and/or target lesion MI.

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Successful Transcatheter Treatment of Left Pulmonary Artery to Left Atrium Communication Diagnosed in Adulthood

Objectives: To describe and report the results of an original technique for trans-femoral (TF) transcatheter-aortic-valve-replacement (TAVR). Background: TF approach represents the commonest TAVR technique. The best technique for TF-TAVR is not recognized. Methods: We developed a less-invasive totally-endovascular (LITE) technique for TF-TAVR. The key aspects are: precise TAVR access puncture using angiographic-guidewire-ultrasound guidance radial approach as the “secondary access” (to guide valve positioning, to check femoral-access hemostasis and to manage eventual access-site complications) non-invasive pacing (by retrograde left ventricle stimulation or by definitive pace-maker external programmer). The LITE technique has been systematically adopted at our Institution. Procedure details, complications and clinical events occurring during hospitalization were prospectively recorded. Major vascular complications and life-threatening or major bleedings were the primary study end-points. Results: A total of 153 consecutive patients referred for TF-TAVR were approached using the LITE technique. Mean predicted surgical operative mortality was 4.9% and mean TAVR predicted mortality was 3.9%. In 132 (86.3%) patients, TAVR was completed without the need for additional femoral artery access or transvenous temporary pace-maker implantation. Major vascular complications occurred in 2 (1.3%), life-threatening or major bleedings occurred in 4 (2.6%) patients. All-cause death occurred in 3 patients (2.0%). Conclusions: TF-TAVR according to LITE technique is feasible and is associated with very low rates of vascular or bleeding complications.