Cardiopulmonary Fitness and Personalized Exercise Prescription in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are generally restricted regarding participation in competitive sports based on the potential risk of sudden cardiac death and malignant arrhythmias. As a result, they are often inactive and experience the negative consequences of a sedentary lifestyle. Hence, the need arises to strike the right balance between these 2 extremes through personalized exercise prescription. The aims of this study were (1) to assess the characteristics of patients with HCM practicing regular aerobic physical activity compared with sedentary patients; (2) to perform a personalized moderate-intensity exercise prescription and evaluate its effects. METHODS AND RESULTS: Patients with HCM were evaluated through clinical assessment, ECG, ambulatory ECG monitoring, echocardiography, and cardiopulmonary testing. A personalized moderate-intensity exercise prescription was performed, and the same investigations were repeated. Physically active patients with HCM demonstrated better cardiopulmonary functional capacity than sedentary patients (oxygen consumptionpeak/kg 32.9±7.4 versus 25.2±7.4 mL/min per kg P≤0.0001, ventilation/carbon dioxide production slope 26.7±4.3 versus 29.9±5.2 P=0.004), with similar prevalence of ventricular arrhythmias (P=0.43). Sedentary subjects showed a borderline higher prevalence of obesity (P=0.07) than physically active subjects. Moderate-intensity exercise prescription led to improved cardiopulmonary fitness without occurrence of adverse events. CONCLUSIONS: Patients with HCM practicing regular aerobic exercise have a better functional capacity in the absence of relevant events than sedentary patients. Conversely, a sedentary lifestyle led to a deterioration of cardiopulmonary functional capacity and fitness. The tailored moderate-intensity personalized exercise prescription appears to be a feasible approach in carefully selected patients with HCM to counterbalance the negative effects of sedentary behavior without significant major events.

Mechanosensing by Piezo1 regulates osteoclast differentiation via PP2A-Akt axis in periodontitis.

Mechanical stimulus to the multicellular bone unit (MBU) plays a key role in normal bone remodeling, whereas disuse osteoporosis, for example, represents loss of bone owing to lack of mechanical stresses. The analogy can be applied to a variety of pathogenic bone lytic complications, including periodontitis, in which local mechanical stress appears to be diminished. The activation of mechanosensitive Piezo1 Ca 2+ channel expressed by osteoblasts and osteocytes in the MBU elicits the osteogenic signals in those cells. However, since osteoclast (OC)-specific Piezo1-gene knockout mice showed no skeletal phenotype, it has been assumed that Piezo1 might not play any role in OC-mediated bone remodeling. Here, however, we showed that mechanical stimulation of Piezo1 expressed on preosteoclasts (pre-OCs) downmodulates OC formation and, hence, bone resorptive activity in periodontitis, accompanied by significantly reduced expression of NFATc1, a master transcription factor for RANKL-induced OC-genesis. We know that the Ca 2+ /calcineurin/NFAT axis upregulates NFATc1 activation in pre-OCs. Interestingly, Piezo1-elicited Ca 2+ influx did not affect NFATc1 expression. Instead, PP2A-mediated dephosphorylation of Akt downregulated NFATc1 in Piezo1-activated pre-OCs. However, systemic administration with Yoda1, a Piezo1 chemical agonist, or local injection of PP2A agonist, significantly downregulated the bone resorption induced in a mouse model of periodontitis, together with reduced numbers of TRAP + /phospho-Akt + pre-OCs in local bone. These results suggest that mechanosensing by Piezo1 expressed on pre-OCs can downmodulate the RANKL-induced OC-genesis via the PP2A/Akt-dephosphorylation pathway, but that such Piezo1-mediated downregulation of bone resorption is attenuated in periodontitis. Significance Statement: The mechanosensitive Ca 2+ channel Piezo1 plays important regulatory roles in a variety of cellular activities. RANKL-mediated OC-genesis requires permissive co-stimulatory signal from ITAM receptors, such as OSCAR and TREM2, to trigger the calcineurin/calmodulin signaling axis via Ca 2+ oscillation, thereby upregulating NFATc1 expression. Activation of Piezo1 remarkably suppressed RANKL-induced NFATc1 activation which, in turn, reduced OC-genesis. Such mechanical activation of Piezo1 expressed on pre-OCs induced intracellular Ca 2+ influx. Nonetheless, PP2A-mediated dephosphorylation of Akt, not the calcineurin/calmodulin pathway, suppressed NFATc1 in RANKL-elicited OC-genesis and resultant bone resorption, both in vitro and in vivo . These results indicate that mechanostress applied to pre-OCs can downregulate pathogenic OC-genesis and that Piezo1, as the mediator, is a novel molecular target for the development of anti-osteolytic therapies.

Children's diet assessed with the Mediterranean Diet Index: the finding of new eating habits and their impact on a cohort of Italian children.

OBJECTIVES: Mediterranean Diet (MD) has been inversely associated with many diseases: it reduces total mortality and lowers cardiovascular risk. Despite the known benefits of MD, variations of dietary habits have occurred in recent years especially in young people. The aim of our study is to evaluate MD adherence in a cohort of Italian children and adolescents living in Southern Italy. METHODS AND RESULTS: Adherence to MD was evaluated with the Mediterranean Diet Index (KIDMED). Sex, age, and anthropometric measures were recorded on a population of 132 children; of those 71.2% showed poor adherence to MD, 26.5% average adherence and only 2.3% good adherence. Higher prevalence of poor adherence was recorded in obese children and there was statistically significant inverse correlation between age and adherence score. CONCLUSIONS: Our results highlight low adherence to MD in a cohort of Italian children. These findings support the importance of monitoring dietary habits, especially in adolescents.

Inhibition of SARS-CoV-2 infection by Porphyromonas gingivalis and the oral microbiome.

The COVID-19 pandemic persists despite the availability of vaccines, and it is, therefore, crucial to develop new therapeutic and preventive approaches. In this study, we investigated the potential role of oral microbiome in SARS-CoV-2 infection. Using an in vitro SARS-CoV-2 pseudovirus infection assay, we found a potent inhibitory effect exerted by Porphyromonas gingivalis on SARS-CoV-2 infection mediated by known P. gingivalis compounds such as phosphoglycerol dihydroceramide (PGDHC) and gingipains as well as by unknown bacterial factors. We found that the gingipain-mediated inhibition of infection is likely due to cytotoxicity, whereas PGDHC inhibited virus infection by an unknown mechanism. Unidentified factors present in P. gingivalis supernatant inhibited SARS-CoV-2 likely via the fusion step of the virus life cycle. We addressed the role of other oral bacteria and found certain periodontal pathogens capable of inhibiting SARS-CoV-2 pseudovirus infection by inducing cytotoxicity on target cells. In the human oral cavity, we observed that the modulatory activity of oral microbial communities varied among individuals, in that some saliva-based cultures were capable of inhibiting while others were enhancing infection. These findings contribute to our understanding of the complex relationship between the oral microbiome and viral infections, offering potential avenues for innovative therapeutic strategies in combating COVID-19. IMPORTANCE: The oral microbiome is important in health and disease, and in this study, we addressed the potential role of the oral microbiome in COVID-19 infection. Our in vitro studies suggest that certain bacteria of the oral microbiome such as P. gingivalis produce compounds that could potentially inhibit SARS-CoV-2 infection. These findings elucidating the interactions between the oral microbiome and SARS-CoV-2 infection will be important in our understanding of COVID-19 pathogenesis and the development of innovative therapeutic and preventive strategies against COVID-19 infection.

Surface Pre-Reacted Glass-Ionomer Eluate Suppresses Osteoclastogenesis through Downregulation of the MAPK Signaling Pathway.

Surface pre-reacted glass-ionomer (S-PRG) is a new bioactive filler utilized for the restoration of decayed teeth by its ability to release six bioactive ions that prevent the adhesion of dental plaque to the tooth surface. Since ionic liquids are reported to facilitate transepithelial penetration, we reasoned that S-PRG applied to root caries could impact the osteoclasts (OCs) in the proximal alveolar bone. Therefore, this study aimed to investigate the effect of S-PRG eluate solution on RANKL-induced OC-genesis and mineral dissolution in vitro. Using RAW264.7 cells as OC precursor cells (OPCs), TRAP staining and pit formation assays were conducted to monitor OC-genesis and mineral dissolution, respectively, while OC-genesis-associated gene expression was measured using quantitative real-time PCR (qPCR). Expression of NFATc1, a master regulator of OC differentiation, and the phosphorylation of MAPK signaling molecules were measured using Western blotting. S-PRG eluate dilutions at 1/200 and 1/400 showed no cytotoxicity to RAW264.7 cells but did significantly suppress both OC-genesis and mineral dissolution. The same concentrations of S-PRG eluate downregulated the RANKL-mediated induction of OCSTAMP and CATK mRNAs, as well as the expression of NFATc1 protein and the phosphorylation of ERK, JNK, and p38. These results demonstrate that S-PRG eluate can downregulate RANKL-induced OC-genesis and mineral dissolution, suggesting that its application to root caries might prevent alveolar bone resorption.

Association of sex with in-hospital management and outcomes of patients with heart failure: Data from the REAL-HF registry.

BACKGROUND: There are sex differences in HF patients. It is not clear whether such differences mainly reflect cultural behaviours and clinical inertia, and the role of sex on clinical outcomes is still controversial. We aimed to investigate the association of sex with in-hospital management and outcomes in patients with HF. METHODS: We analyzed data of 4016 adult patients hospitalized for HF in 2020 to 2021 and enrolled in a multicentre national registry. RESULTS: Women (n = 1,818 [45%]) were older than men (83 vs 77 years, P < .0001), with a higher prevalence of arterial hypertension (73% vs 69%, P = .011) and atrial fibrillation. Women presented more frequently with HF and preserved ejection fraction -HFpEF (55% vs 32%, P < .001). They were more often hospitalized in internal medicine departments (71% vs 51%), and men in highly specialized cardiology units (49% vs 29%). When considering HF pharmacological treatments at discharge in the subgroup with reduced ejection fraction -HFrEF (n=1525), there were no significant differences (49% of women treated with GDMT [guideline-directed medical therapy] vs 52% of men, P = .197). Sex was not associated either with hospital readmissions (30-days OR [95% CI] = 0.89 [0.71-1.11], P = .304; 1-year OR [95% CI] = 1.02[0.88-1.19], P = .777) or with mortality (in-hospital OR [95% CI] = 1.14 [0.73-1.78], P = .558; 1-year OR [95% CI] = 1.08 [0.87-1.33], P = .478). Similar results were obtained when considering different HF categories based on left ventricular ejection fraction. CONCLUSIONS: Women and men exhibited distinct clinical profiles. Although this may have had an impact on hospital pathways (noncardiology/cardiology units) and pharmacological prescriptions, sex per se did not appear as an independent determinant of clinical choices. Moreover, when considering homogeneous groups, women were not undertreated. Finally, female sex was not associated with worse clinical outcomes.

Multimodality imaging for the evaluation and management of patients with long-term (durable) left ventricular assist devices.

Left ventricular assist devices (LVADs) are gaining increasing importance as therapeutic strategy in advanced heart failure (HF), not only as bridge to recovery or to transplant but also as destination therapy. Even though long-term LVADs are considered a precious resource to expand the treatment options and improve clinical outcome of these patients, these are limited by peri-operative and post-operative complications, such as device-related infections, haemocompatibility-related events, device mis-positioning, and right ventricular failure. For this reason, a precise pre-operative, peri-operative, and post-operative evaluation of these patients is crucial for the selection of LVAD candidates and the management LVAD recipients. The use of different imaging modalities offers important information to complete the study of patients with LVADs in each phase of their assessment, with peculiar advantages/disadvantages, ideal application, and reference parameters for each modality. This clinical consensus statement sought to guide the use of multimodality imaging for the evaluation of patients with advanced HF undergoing LVAD implantation.

Dapagliflozin Effects on Cardiac Deformation in Heart Failure and Secondary Clinical Outcome.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors were shown to reduce morbidity and mortality in patients with heart failure. OBJECTIVES: This study aims to assess potential effects of dapagliflozin in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF) and heart failure with mildly reduced ejection fraction (HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). METHODS: This randomized, prospective, single-center, open-label trial compared consecutive nondiabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except sodium-glucose cotransporter type 2 inhibitors. Primary endpoint was the presence of a significant modification of left ventricular global longitudinal strain, diastolic function (as peak atrial longitudinal strain) and right ventricular function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. RESULTS: Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n = 44) or to continue with OMT (n = 44). All STE values improved in the dapagliflozin group after 6 months, whereas there was a nonsignificant improvement in OMT group. Moreover, when comparing the modification of STE parameters at follow-up in patients with HFrEF and HFmrEF, only the main treatment effect resulted statistically significant in both groups (P < 0.0001), indicating a significant difference between dapagliflozin and OMT. CONCLUSIONS: This study provided randomized data on the beneficial effect of dapagliflozin in nondiabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique, ie, STE. This suggests its usefulness for left ventricular reverse remodeling and better quality of life in patients with HFrEF and HFmrEF. (Effects of Dapagliflozin on cardiac deformation and clinical outcomes in heart failure with reduced and mildly reduced ejection fraction [DAPA ECHO trial]; EudraCT number: 2021-005394-66).

Potential Role of Left Atrial Strain to Predict Atrial Fibrillation Recurrence after Catheter Ablation Therapy: A Clinical and Systematic Review.

Pulmonary vein isolation (PVI) with catheter ablation (CA) represents an effective therapy for atrial fibrillation (AF). Unfortunately, it is still not exempt from severe complications. The balance of risks and benefits should be assessed, and a patient-tailored approach is desirable. So far, several clinical and cardiac imaging parameters have been evaluated to investigate pre- and post-procedural features that could help clinicians in the selection of patients at high risk of a poor outcome after CA. This clinical and systematic review analyses the potential role of new LA parameters, such as LA reservoir strain, to predict AF recurrence after CA therapy. Notably, LA reservoir strain gains substantial clinical importance in patients with paroxysmal AF and when a low CHADS2-VASc score is retrieved. LA reservoir strain provides data concerning the risk of AF recurrence after PVI and, thus, in the management of long-term medical therapy in this patient's group.

Atrial Fibrillation, Atrial Myopathy, and Thromboembolism: The Additive Value of Echocardiography and Possible New Horizons for Risk Stratification.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, and it is associated with increased stroke and dementia risk. While the established paradigm attributes these complications to blood stasis within the atria and subsequent thrombus formation with cerebral embolization, recent evidence suggests that atrial myopathy (AM) may play a key role. AM is characterized by structural and functional abnormalities of the atria, and can occur with or without AF. Moving beyond classifications based solely on episode duration, the 4S-AF characterization has offered a more comprehensive approach, incorporating patient's stroke risk, symptom severity, AF burden, and substrate assessment (including AM) for tailored treatment decisions. The "ABC" pathway emphasizes anticoagulation, symptom control, and cardiovascular risk modification and emerging evidence suggests broader benefits of early rhythm control strategies, potentially reducing stroke and dementia risk and improving clinical outcomes. However, a better integration of AM assessment into the current framework holds promise for further personalizing AF management and optimizing patient outcomes. This review explores the emerging concept of AM and its potential role as a risk factor for stroke and dementia and in AF patients' management strategies, highlighting the limitations of current risk stratification methods, like the CHA2DS2-VASc score. Echocardiography, particularly left atrial (LA) strain analysis, has shown to be a promising non-invasive tool for AM evaluation and recent studies suggest that LA strain analysis may be a more sensitive risk stratifier for thromboembolic events than AF itself, with some studies showing a stronger association between LA strain and thromboembolic events compared to traditional risk factors. Integrating it into routine clinical practice could improve patient management and targeted therapies for AF and potentially other thromboembolic events. Future studies are needed to explore the efficacy and safety of anticoagulation in AM patients with and without AF and to refine the diagnostic criteria for AM.

The Role of Speckle Tracking Echocardiography in the Evaluation of Advanced-Heart-Failure Patients.

Health care is currently showing a fall in heart failure (HF) incidence and prevalence, particularly in developed countries, but with only a subset receiving appropriate therapy to protect the heart against maladaptive processes such as fibrosis and hypertrophy. Appropriate markers of advanced HF remain unidentified, which would help in choosing the most suitable therapy and avoid major compliance problems. Speckle tracking echocardiography (STE) is a good choice, being a non-invasive imaging technique which is able to assess cardiac deformation in a variety of conditions. Several multicenter studies and meta-analyses have demonstrated the clinical application and accuracy of STE in early and late stages of HF, as well as its association with both left ventricular (LV) filling pressures and myocardial oxygen consumption. Furthermore, STE assists in assessing right ventricular free-wall longitudinal strain (RVFWLS), which is a solid predictor of right ventricle failure (RVF) following LV assist device (LVAD) implantation. However, STE is known for its limitations; despite these, it has been shown to explain symptoms and signs and also to be an accurate prognosticator. The aim of this review is to examine the advantages of STE in the early evaluation of myocardial dysfunction and its correlation with right heart catheterization (RHC) parameters, which should have significant clinical relevance in the management of HF patients.

Stress echocardiography in heart failure patients: additive value and caveats.

Heart failure (HF) is a clinical syndrome characterized by well-defined signs and symptoms due to structural and/or myocardial functional impairment, resulting in raised intracardiac pressures and/or inadequate cardiac stroke volume at rest or during exercise. This could derive from direct ischemic myocardial injury or other chronic pathological conditions, including valvular heart disease (VHD) and primary myocardial disease. Early identification of HF etiology is essential for accurate diagnosis and initiation of early and appropriate treatment. Thus, the presence of accurate means for early diagnosis of HF symptoms or subclinical phases is fundamental, among which echocardiography being the first line diagnostic investigation. Echocardiography could be performed at rest, to identify overt structural and functional abnormalities or during physical or pharmacological stress, in order to elicit subclinical myocardial function impairment e.g. wall motion abnormalities and raised ventricular filling pressures. Beyond diagnosis of ischemic heart disease, stress echocardiography (SE) has recently shown its unique value for the evaluation of diastolic heart failure, VHD, non-ischemic cardiomyopathies and pulmonary hypertension, with recommendations from international societies in several clinical settings. All these features make SE an important additional tool, not only for diagnostic assessment, but also for prognostic stratification and therapeutic management of patients with HF. In this review, the unique value of SE in the evaluation of HF patients will be described, with the objective to provide an overview of the validated methods for each setting, particularly for HF management.

Physical exercise in hypertensive heart disease: From the differential diagnosis to the complementary role of exercise.

Arterial hypertension (AH) is one of the most common pathologic conditions and uncontrolled AH is a leading risk factor for cardiovascular disease and mortality. AH chronically causes myocardial and arterial remodelling with hemodynamic changes affecting the heart and other organs, with potentially irreversible consequences leading to poor outcomes. Therefore, a proper and early treatment of AH is crucial after the diagnosis. Beyond medical treatment, physical exercise also plays a therapeutic role in reducing blood pressure, given its potential effects on sympathetic tone, renin-angiotensin-aldosterone system, and endothelial function. International scientific societies recommend physical exercise among lifestyle modifications to treat AH in the first stages of the disease. Moreover, some studies have also shown its usefulness in addition to drugs to reduce blood pressure further. Therefore, an accurate, personalized exercise prescription is recommended to optimize the prevention and treatment of hypertension. On the other hand, uncontrolled AH in athletes requires proper risk stratification and careful evaluation to practice competitive sports safely. Moreover, the differential diagnosis between hypertensive heart disease and athlete's heart is sometimes challenging and requires a careful and comprehensive interpretation in order not to misinterpret the clinical findings. The present review aims to discuss the relationship between hypertensive heart disease and physical exercise, from diagnostic tools to prevention and treatment strategies.

Myocardial Work Indices Predict Hospitalization in Patients with Advanced Heart Failure.

BACKGROUND: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW's feasibility in the prognostic stratification of AdHF. METHODS: We retrospectively screened patients with AdHF who accessed our hospital in 2018-2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). RESULTS: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50-62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323-868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan-Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. CONCLUSIONS: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

Hypertriglyceridemia: Molecular and Genetic Landscapes.

Lipid disorders represent one of the most worrisome cardiovascular risk factors. The focus on the impact of lipids on cardiac and vascular health usually concerns low-density lipoprotein cholesterol, while the role of triglycerides (TGs) is given poor attention. The literature provides data on the impact of higher plasma concentrations in TGs on the cardiovascular system and, therefore, on the outcomes and comorbidities of patients. The risk for coronary heart diseases varies from 57 to 76% in patients with hypertriglyceridemia. Specifically, the higher the plasma concentrations in TGs, the higher the incidence and prevalence of death, myocardial infarction, and stroke. Nevertheless, the metabolism of TGs and the exact physiopathologic mechanisms which try to explain the relationship between TGs and cardiovascular outcomes are not completely understood. The aims of this narrative review were as follows: to provide a comprehensive evaluation of the metabolism of triglycerides and a possible suggestion for understanding the targets for counteracting hypertriglyceridemia; to describe the inner physiopathological background for the relationship between vascular and cardiac damages derived from higher plasma concentrations in TGs; and to outline the need for promoting further insights in therapies for reducing TGs plasma levels.

Echocardiographic and clinical features of patients developing prosthesis-patient mismatch after transcatheter aortic valve replacement: Insights from the Recovery-TAVR registry.

BACKGROUND: The impact of prosthesis-patient mismatch (PPM) on major endpoints after transcatheter aortic valve replacement (TAVR) is controversial and the effects on progression of heart damage are poorly investigated. Therefore, our study aims to evaluate the prevalence and predictors of PPM in a "real world" cohort of patients at intermediate and low surgical risk, its impact on mortality and the clinical-echocardiographic progression of heart damage. METHODS: 963 patients who underwent TAVR procedure between 2017 and 2021, from the RECOVERY-TAVR international multicenter observational registry, were included in this analysis. Multiparametric echocardiographic data of these patients were analyzed at 1-year follow-up (FU). Clinical and echocardiographic features were stratified by presence of PPM and PPM severity, as per the most current international recommendations, using VARC-3 criteria. RESULTS: 18% of patients developed post-TAVR. PPM, and 7.7% of the whole cohort had severe PPM. At baseline, 50.3% of patients with PPM were male (vs 46.2% in the cohort without PPM, P = .33), aged 82 (IQR 79-85y) years vs 82 (IQR 78-86 P = .46), and 55.6% had Balloon-Expandable valves implanted (vs 46.8% of patients without PPM, P = .04); they had smaller left ventricular outflow tract (LVOT) diameter (20 mm, IQR 19-21 vs 20 mm, IQR 20-22, P = .02), reduced SVi (34.2 vs 38 mL/m2, P < .01) and transaortic flow rate (190.6 vs 211 mL/s, P < .01). At predischarge FU patients with PPM had more paravalvular aortic regurgitation (moderate-severe AR 15.8% vs 9.2%, P < .01). At 1-year FU, maladaptive alterations of left ventricular parameters were found in patients with PPM, with a significant increase in end-systolic diameter (33 mm vs 28 mm, P = .03) and a significant increase in left ventricle end systolic indexed volume in those with moderate and severe PPM (52 IQR 42-64 and 52, IQR 41-64 vs 44 IQR 35-59 in those without, P = .02)). No evidence of a significant impact of PPM on overall (P = .71) and CV (P = .70) mortality was observed. Patients with moderate/severe PPM had worse NYHA functional class at 1 year (NYHA III-IV 13% vs 7.8%, P = .03). Prosthesis size≤23 mm (OR 11.6, 1.68-80.1) was an independent predictor of PPM, while SVi (OR 0.87, 0.83-0.91, P < .001) and LVOT diameter (OR 0.79, 0.65-0.95, P = .01) had protective effect. CONCLUSIONS: PPM was observed in 18% of patients undergoing TAVR. Echocardiographic evaluations demonstrated a PPM-related pattern of early ventricular maladaptive alterations, possibly precursor to a reduction in cardiac function, associated with a significant deterioration in NYHA class at 1 year. These findings emphasize the importance of prevention of PPM of any grade in patients undergoing TAVR procedure, especially in populations at risk.