Funding Acknowledgements Type of funding sources: None. Background. There are limited data about the intraprocedural hemodynamic study performed immediately before and after transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis (AS). Purpose. We aimed to evaluate the acute hemodynamic impact of TAVI in patients with severe AS and to investigate invasive and non-invasive parameters predicting all-cause mortality. Methods. A total of 245 consecutive AS patients 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. Results. LHC after TAVI revealed significant changes in aortic and 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/sec, p˂0.001; Figure 1A) and negative dP/dT (1310.7± 431.1 vs 1075.1 ± 440.8 mmHg/sec, p˂0.001; Figure 1B). Post TAVI echo showed a significant reduction in LV end diastolic volume index (54.6 ± 18.4 ml/m2 vs 51.7 ± 17.5 ml/m2; p = 0.017; Figure 1C), improvement in left ventricle ejection fraction (from 55 ± 12 to 57.2 ± 10.5%, p˂0.001; Figure 1D) and pulmonary artery systolic pressure (42.1 ± 14.2 vs 33.1 ± 10.7 mmHg, p < 0.001; Figure 1E). After a mean follow-up time interval of 24 months, 47 patients died. Post-TAVI aortic regurgitation (2- 3- 4+) at echocardiography was the only independent predictor of mortality (HR 4.43, C.I. 1,71 – 11,45, p = 0.002; Figure 2). Conclusions. LHC performed immediately before and after prosthesis release offers a unique insight in the assessment ofLV adaptation to severe AS and the impact of TAVI on LV, catching changes in indexes of intrinsic contractility and myocardial relaxation. Aortic regurgitation assessed by echocardiography was the only independent predictor of mortality in patients undergoing TAVI. FIGURE LEGEND Figure 1. A-B: Impact of TAVI on haemodynamic parameters: Box plot with median and interquartile ranges of positive dP/dT and negative dP/dT values pre vs post TAVI. C-D-E: Impact of TAVI on echocardiographic parameters: Box plot with median and interquartile ranges of left ventricular end diastolic volume index (LVEDVi), left ventricular ejection fraction (EF) and pulmonary artery systolic pressure (PASP) values pre vs post TAVI. Figure 2. Kaplan-Meier curves for survival showing that AR (2-3-4+) assessed with echocardiography had the strongest association with mortality. Abstract Figure 1.  Abstract Figure 2.

Background Global longitudinal strain (LS) is a sensitive marker of ischemic myocardial damage and predicts adverse left ventricular (LV) remodeling and outcome, independently of infarct size. In healthy subjects, regional LS increases from LV base to apex and enhances under physical or pharmacological stress, while in ST-elevation myocardial infarction (STEMI), response to dobutamine depends on transmurality of necrosis. It is known that coronary flow reserve during adenosine (ADN) is impaired both in ischemic and remote myocardium, but effect of ADN on strain reserve has never been investigated. Similarly, LS response to ADN in ischemic (iLS) and remote (rLS) myocardium and their relative contribution to LV function and remodeling are still unknown. Methods 61 consecutive patients with first STEMI (26 anterior, 29 inferior, 6 lateral), treated by successful primary percutaneous coronary intervention (PCI) followed by PCI of non-culprit coronary arteries, underwent rest and stress ADN (140 mcg/kg/minutes in 90 seconds) echocardiography at discharge (7 ± 2 days after admission). LV end-diastolic volume indexed for body surface area (EDV), ejection fraction (EF) and wall motion score index (WMSI) were measured at rest, while GLS, iLS and rLS analysis was performed both at rest and during stress. Ischemic and remote myocardium was allocated, by standard LV segmentation, basing on the culprit coronary artery. Results Significant differences existed among anterior, inferior and lateral STEMI in median (iQr) EDV [52 (45-59) vs 45 (36-51) vs 48 (45–56) ml, respectively, p=.034 overall], EF [47 (37-58) vs 58 (53–61) vs 56 (46-60)%, respectively, p=.002 overall], WMSI [1.63 (1.38–2) vs 1.25 (1.19-1.47) vs 1.41 (1.30-1.75), respectively, p=.001 overall]. GLS differed among anterior, inferior and lateral STEMI both at rest [13.75 (11.63-16.1) vs 19.5 (17.15-22.4) vs 17.85 (17.02-19), respectively, p<.001 overall] and during ADN [14 (12.35-16.15) vs 19.5 (17.9–22.05) vs 15.95 (14.40-19.48), respectively, p<.001], but did not change within groups. No differences were found between rest and stress iLS in any group. Similarly, rLS remained unchanged in anterior and inferior STEMI, and impaired after ADN in lateral STEMI [15.90 (11.45-18) at stress vs 16.8 (15.25-19.2) at rest, p=.043]. Inferior STEMI showed better iLS than anterior STEMI both at rest [17 (15.1–19.9) vs 13.75 (11.46-16.92), respectively, p=.001] and during stress [16.2 (15–20.4) vs 14.42 (12.67-15.83), respectively, p=.001]. Conclusions In the subacute phase of STEMI, GLS, iLS and rLS are heterogeneous and depend on infarct site. After ADN, there is no strain reserve in ischemic neither in remote myocardium. This may reflect regional differences in the response of microcirculation and myocardium to ischemia or may underlie pre-existing pathophysiological differences in the coronary circulation

Objective: Microvascular angina (MVA) is characterized by functional and structural alterations of resistance coronary arteries without any significant alterations of epicardial coronary arteries. Whether MVA patients present also dysfunction of peripheral resistance arteries is still a matter of debate. We sought to evaluate whether MVA is associated with parameters of systemic microvascular dysfunction. Design and method: Thirteen patients with MVA and 13 healthy control subjects were enrolled in this study. The diagnosis of MVA was based on the presence of typical symptoms of ischemic heart disease, evidence of myocardial ischemia on exercise stress testing and normal epicardial coronary arteries at angiography. Parameters of peripheral microvascualar alterations, arterial stiffness (Pulse Wave Velocity, PWV), and central blood pressure (cBP) and Subendocardial Viability Ratio (SEVR, and index of subendocardial microvascular dysfunction), were evaluated by applanation tonometry. Results: Patients and controls were similar with respect to metabolic parameters, BMI, and renal function. MVA patients were on therapy with beta-blockers (50%), calcium channel blockers (37%), nitrates (12%), renin-angiotensin-blockers (44%), and statins (25%). MVA patients were slightly older than controls (63.6 ± 1.9 vs 53.1 ± 2.0 years, p < 0.05). Albeit in the normal range, peripheral (pSBP) and central (cSBP) systolic BP were significantly higher in MVA patients as compared to controls (pSBP:134.3 ± 2.9 vs 118.5 ± 3.5 mmHg, p < 0.002; and cSBP:124.8 ± 2.9 vs 109.7 ± 2.9 mmHg, p < 0.001). Diastolic BP was similarly preserved in both groups. SEVR, an index of subendocardial microvascular dysfunction, was lower in MVA patients as compared to controls (139.7 ± 4.1 vs 160.4 ± 8.5 %, p < 0.05). Augmentation index (AI), reflected (RPH), and forward (FPH) pulse height, all parameters of peripheral microvascular dysfunction, were also altered in MVA patients as compared to controls (AI:29.0 ± 1.0 vs 19.9 ± 2.4%, p < 0.003; RPH:22.3 ± 1.4 vs 15.3 ± 0.9 mmHg, p < 0.001; FPH:31.0 ± 1.4 vs 24.2 ± 1.4 mmHg p < 0.005). The index of aortic stiffness PWV was similar in both groups (7.20 ± 07 vs 6.6 ± 0.2 m/sec, NS). Conclusions: Patients with MVA on optimal anti-schemic therapy exhibit alterations of parameters of both subendocardial and peripheral microvascular dysfunction, suggesting that coronary microvascular dysfunction is part of a more generalized disorder also involving peripheral resistance arteries.

Funding Acknowledgements Type of funding sources: None. Background Coronary microvascular dysfunction (CMD) occurs before left ventricular hypertrophy (LVH) in Anderson Fabry Disease (AFD). Few data exist about the role of CMD in Fabry cardiomyopathy, when overt LVH has already established. Purpose Aim of our study was to assess the relationship between CMD and clinical and echocardiographic features in a cohort of Fabry cardiomyopathy patients. Methods We performed coronary CT scan to exclude epicardial coronary artery disease (CAD) in 27 AFD cardiomyopathy patients with angina and/or evidence of silent ischemia at treadmill stress test. All consenting patients with no CAD (n = 17) were submitted to resting and stress 13N-Ammonia myocardial perfusion PET/CT to assess the presence of CMD. All patients also underwent complete echocardiography. Patients were followed-up for 17.3 ± 12.5 months. Results Global coronary flow reserve (CFR) resulted &lt;2.5 in 7 (41%) patients. Global stress myocardial blood flow (MBF) was &lt;1.85 mL/min/g in 5 (29%) patients. Global transmural perfusion gradient (TPG, subendocardial MBF/subepicardial MBF) during stress was &lt;1.0 in 13/17 (76.5%) patients. Resting global TPG was ≥1 in 16 (94%) patients. Patients with CFR &lt; 2.5 were older (p = 0.02), had more severe LVH (maximal wall thickness p = 0.04), worst global longitudinal strain (p = 0.03) and E/e’ (p = 0.04) and higher troponin levels (p = 0.002) as compared to patients with CFR ≥ 2.5. They also performed less at treadmill stress (METs p = 0.045). No variables were associated to major cardiovascular events at multivariable analysis. Conclusions In Fabry cardiomyopathy patients with angina and/or evidence of silent ischemia, the prevalence of CMD is high and it is associated to a more severe cardiac phenotype, including cardiac biomarker and functional capacity. We are not able to draw any conclusion on the possible prognostic role of CMD in Fabry cardiomyopathy.