Prolonged Time-to-antihypertensive Therapy Worsens Organ Damage and Blood Pressure Control in Arterial Hypertension.

INTRODUCTION: Delay in arterial hypertension (AH) diagnosis and late therapy initiation may affect progression towards hypertensive-mediated organ damage (HMOD) and blood pressure (BP) control. AIM: We aimed to assess the impact of time-to-therapy on BP control and HMOD in patients receiving AH diagnosis. METHODS: We analysed data from the Campania Salute Network, a prospective registry of hypertensive patients (NCT02211365). At baseline visit, time-to-therapy was defined as the interval between the first occurrence of BP values exceeding guidelines-directed thresholds and therapy initiation; HMOD included left ventricular hypertrophy (LVH), carotid plaque, or chronic kidney disease. Optimal BP control was considered for average values < 140/90 mmHg. Low-risk profile was defined as grade I AH without additional cardiovascular risk factors. RESULTS: From 14,161 hypertensive patients, we selected 1,627 participants who were not on antihypertensive therapy. This population was divided into two groups based on the median time-to-therapy (≤ 2 years n = 1,009, > 2 years n = 618). Patients with a time-to-therapy > 2 years had higher risk of HMOD (adjusted odds ratio, aOR:1.51, 95%, CI:1.19-1.93, p < 0.001) due to increased risks of LVH (aOR:1.43, CI:1.12-1.82, p = 0.004), carotid plaques (aOR:1.29, CI:1.00-1.65, p = 0.047), and chronic kidney disease (aOR:1.68, CI:1.08-2.62, p = 0.022). Time-to-therapy > 2 years was significantly associated with uncontrolled BP values (aOR:1.49, CI:1.18-1.88, p < 0.001) and higher number of antihypertensive drugs (aOR:1.68, CI:1.36-2.08, p < 0.001) during follow-up. In low-risk subgroup, time-to-therapy > 2 years did not impact on BP control and number of drugs. CONCLUSIONS: In hypertensive patients, a time-to-therapy > 2 years is associated with HMOD and uncontrolled BP.

Antiplatelet Therapy in Patients Requiring Oral Anticoagulation and Undergoing Percutaneous Coronary Intervention.

Dual antiplatelet therapy with aspirin and a P2Y12 inhibitor is fundamental in all patients undergoing percutaneous coronary intervention (PCI) to prevent coronary thrombosis. In patients with atrial fibrillation (AF), an oral anticoagulant gives protection against ischemic stroke or systemic embolism. AF-PCI patients are at high bleeding risk and decision-making regarding the optimal antithrombotic therapy remains challenging. Dual antithrombotic therapy (DAT) has been shown to reduce bleeding events but at the cost of a higher risk of stent thrombosis. Further studies are needed to clarify the optimal duration of triple antithrombotic therapy (TAT) or DAT and the role of more potent antiplatelet drugs.

N-palmitoyl-d-glucosamine limits mucosal damage and VEGF-mediated angiogenesis by PPARα-dependent suppression of pAkt/mTOR/HIF1α pathway and increase in PEA levels in AOM/DSS colorectal carcinoma in mice.

Chronic intestinal inflammation and neo-angiogenesis are interconnected in colorectal carcinoma (CRC) pathogenesis. Molecules reducing inflammation and angiogenesis hold promise for CRC prevention and treatment. N-Palmitoyl-d-glucosamine (PGA), a natural glycolipid analog with anti-inflammatory properties, has shown efficacy against acute colitis. Micronized PGA (mPGA) formulations exhibit superior anti-inflammatory activity. This study investigates the in vivo anti-angiogenic and protective effects of mPGA in a mouse model of colitis-associated CRC induced by azoxymethane/dextran sodium sulfate (AOM/DSS). CRC was induced in C57BL/6J mice using intraperitoneal azoxymethane followed by three cycles of 2.5% dextran sodium sulfate (DSS) in drinking water. Mice were treated with mPGA (30-150 mg/kg) with or without the PPARα inhibitor MK886 (10 mg/kg). At Day 70 post-azoxymethane injection, mice underwent anesthetized endoscopic colon evaluation. Post-mortem analysis of tumorigenesis and angiogenesis was performed using histological, immunohistochemical, and immunoblotting techniques. mPGA improved disease progression and survival rates in a dose- and PPARα-dependent manner in AOM/DSS-exposed mice. It reduced polyp formation, decreased pro-angiogenic CD31, pro-proliferative Ki67, and pro-inflammatory TLR4 expression levels, and inhibited VEGF and MMP-9 secretion by disrupting the pAkt/mTOR/HIF1α pathway. mPGA increased colon PEA levels, restoring anti-tumoral PPARα and wtp53 protein expression. Given its lack of toxicity, mPGA shows potential as a nutritional intervention to counteract inflammation-related angiogenesis in CRC.

Sex-Related Differences in Left Ventricular Geometry Patterns in Patients With Arterial Hypertension.

Background: Sex-specific differences in left ventricular (LV) geometry might help in developing tailored strategies for hypertension management. Objectives: The purpose of the study was to evaluate sex-related differences in LV geometry at baseline and over time in hypertension. Methods: From a prospective registry, we included hypertensives without prevalent cardiovascular disease, incident myocardial infarction, chronic kidney disease > stage III, and with normal LV ejection fraction. LV mass index >115 g/m2 in males and >95 g/m2 in females, identified LV hypertrophy (LVH). Relative wall thickness ≥0.43 defined LV concentric geometry. LVH in presence of concentric geometry was defined as concentric LVH, whereas relative wall thickness <0.43 was categorized as eccentric. Concentric geometry, or LVH, identified LV remodeling. Results: Six thousand four hundred twenty-seven patients (age 53 ± 11 years, 43% females) were included. At baseline, females showed lower prevalence of normal geometric pattern and higher prevalence of LVH than males (50% vs 72%, P < 0.001; 47% vs 23%, P < 0.001, respectively), with a higher prevalence of eccentric LVH (40% vs 18%, P < 0.001). Female sex was independently associated with LV remodeling (OR: 2.36; 95% CI: 2.12-2.62; P < 0.001). At long-term follow-up (mean 6.1 years, IQR: 2.8-8.6 years), prevalence of LV remodeling increased in both sexes, although a normal LV geometry remained less frequent in females than males (43% vs 67%, P < 0.001), with differences persisting in eccentric (41% vs 21%, P < 0.001) and concentric LVH (11% vs 5%, P < 0.001). Conclusions: We found sex-related differences in LV geometry among hypertensives. Females have higher risk of LV remodeling at baseline compared with males, with differences persisting at long-term follow-up.

Carotid plaque offsets sex-related differences in cardiovascular risk of young hypertensive patients.

BACKGROUND: Women have a lower risk for cardiovascular (CV) disease compared to men. Whether this difference is influenced by the presence of hypertension-mediated organ damage is unknown. OBJECTIVE: To assess whether the presence of carotid plaque (CP) impacts the sex difference in risk for CV events in treated hypertensive patients. METHODS: From the Campania Salute Network Registry 2419 women and men <51 years of age with treated hypertension and free from prevalent CV disease were included. The presence of CP was identified by Doppler ultrasound (intima-media thickness≥1.5 mm). The primary outcome was a composite of fatal and non-fatal stroke or myocardial infarction, sudden death, TIA, myocardial revascularization, de novo angina, and atrial fibrillation. RESULTS: Among patients without CP at baseline (n = 1807), women were older, with higher systolic blood pressure, serum cholesterol level and prevalence of LVH but lower serum triglycerides and eGFR, compared to men (all p < 0.001). Among patients with CP (n = 612), women were older, used higher number of antihypertensive drugs, had higher serum cholesterol level and prevalence of left ventricular hypertrophy (LVH), but had lower serum triglycerides and eGFR compared to men (all p < 0.001). During follow-up, women without CP had a lower risk for CV disease than men (hazard ratio, HR, 0.51, 95 % confidence intervals, CI, 0.27-0.99, p = 0.04) after accounting for cardiovascular risk factors, LVH, and antihypertensive treatment. In contrast, among patients with CP, women had similar risk for CV disease compared with men (HR 1.3, 95 % CI, 0.59-2.9, p = 0.48). CONCLUSIONS: Our findings suggest that the presence of CP in young patients with treated hypertension offsets the CV disease protection in women. TRIAL REGISTRATION: NCT02211365.

Safety and Efficacy of Combined Coronary and Peripheral Percutaneous Revascularization: A Proof-of-Concept Study.

Background. Lower extremity peripheral artery disease (LEPAD) frequently coexists with coronary artery disease (CAD) in patients with multisite vascular disease (MVD). While percutaneous revascularization is well-established for both LEPAD and CAD, limited evidence exists for patients eligible for both procedures. Specifically, the feasibility of concomitant LEPAD and CAD percutaneous revascularization remains unknown. Objectives. To compare the efficacy and safety of concomitant coronary and lower extremity elective percutaneous revascularization. Methods. Between 2012 and 2021, we included 135 patients in an observational, retrospective single-center registry. The population was stratified into two groups: 45 patients (concomitant group) underwent simultaneous coronary and peripheral percutaneous interventions, and 90 patients (deferred group) underwent two separate procedures within one year. The primary efficacy endpoint was major adverse cardiovascular events (MACE) at one year, while the primary safety endpoint was in-hospital contrast-induced nephropathy (CIN). Results. Study groups were well-balanced in baseline characteristics. In terms of coronary features, the concomitant revascularization group more often underwent single-vessel percutaneous coronary intervention (PCI), while the deferred group had multivessel PCI with diffuse coronary disease. No differences were detected in the number of LEPAD lesions between groups. For the primary efficacy endpoint, the incidence of MACE at one year was 37.8% in the concomitant group vs. 34.4% in the deferred group (HR 1.20, 95% CI 0.64-2.10; p = 0.61). No significant differences were found in CIN occurrence between the concomitant and deferred groups (11.1% vs. 8.9%; OR 1.30; 95% CI 0.36-4.21; p = 0.68). Conclusions. Multisite vascular disease patients eligible for CAD and LEPAD percutaneous revascularization exhibited a high cardiovascular risk profile with diffuse multivessel coronary and lower extremity disease. Our study suggests the efficacy and safety of concomitant coronary and lower extremity percutaneous revascularization based on one-year MACE incidence and in-hospital CIN. However, dedicated studies are warranted to confirm the short- and long-term outcomes of the concomitant revascularization strategy.

Quantitative flow ratio for the functional assessment of extracranial internal carotid artery stenosis.

BACKGROUND: In asymptomatic patients presenting with significant internal carotid artery (ICA) stenoses undergoing endovascular revascularization, a selective angiography before stenting (CAS) is required. Sometimes, angiographic findings could be discordant from non-invasive assessment and a tool able to evaluate functional relevance of the stenosis could be of value. We sought to evaluate the usefulness of quantitative flow ratio (QFR) as angiography-based tool for functional assessment of ICA stenoses. METHODS: We prospectively enrolled 50 asymptomatic patients undergoing CAS. Peak systolic velocity (PSV, cm/s) assessed at color Doppler echocardiography was used to identify significant stenoses (PSV >125 cm/s). At angiography, assessment of ICA stenosis was obtained visually (%DSVISUAL) and according NASCET criteria (%DSNASCET). Stenoses were considered significant if >60%. After exclusion of 20 vessels, QFR, area stenosis (AS, %) and minimal lumen area (MLA, mm2) were obtained in the remaining 80 vessels. RESULTS: At linear regression analysis, QFR significantly correlated with PSV (r2=0.52, P<0.001) as well as with %DSNASCET (r2=0.68, P<0.001) and %DSVISUAL (r2=0.71, P<0.001). Using PSV as reference, QFR showed good accuracy to predict functionally significant stenosis (AUC=0.98, P<0.001) with a cut-off value of 0.93. As compared with %DSNASCET and %DSVISUAL, QFR showed a significantly higher accuracy (61% vs. 73% vs. 94%, respectively; P<0.05), sensitivity (43% vs. 61% vs. 93%, respectively; P<0.05) and negative predictive value (46% vs. 51% vs. 85%, respectively; P<0.05) for detecting hemodynamically significant ICA stenoses. CONCLUSIONS: This study suggest the potential benefit of adopting QFR for functional assessment of extracranial ICA stenoses. These data should be validated in larger studies.

Application of the 2016 ASE-EACVI Criteria for the Assessment of Diastolic Function in Arterial Hypertension.

INTRODUCTION: No data are available on the diagnostic algorithms recommended by guidelines for the assessment of diastolic dysfunction (DD) in patients with arterial hypertension. AIM: To fill this gap, we evaluated diastolic function in hypertensive patients with and without LVH matched with healthy subjects by applying 2016 American Society of Echocardiography-European Association of Cardiovascular Imaging Guidelines for the evaluation of LV diastolic function. METHODS: 717 healthy and hypertensives with normal LV ejection fraction and with and without LV hypertrophy (LVH), matched 1:1:1 from two prospective registries, represented the study population. RESULTS: By applying algorithm A, indeterminate pattern was found in 0.4% of healthy, in 6.3% of hypertensives without LVH, and in 21% with LVH (overall p < 0.05 vs. healthy). DD was absent in healthy, however present in 2 and 8% of hypertensives without and with LVH (p = 0.06 and p = 0.001 vs. healthy, respectively). By applying algorithm B, no cases of indeterminate pattern were found. DD was observed in 2.9% of healthy, 7 and 10.5% of hypertensives without and with LVH (p < 0.05 vs. healthy). CONCLUSIONS: The use of algorithm A should be limited only to truly normal subjects, whereas algorithm B should be applied to all patients with hypertension, even without comorbidities and irrespective of LVH.

Focus on Prevention: Peripheral Arterial Disease and the Central Role of the Cardiologist.

Peripheral artery disease (PAD) is a manifestation of systemic atherosclerotic disease. PAD patients have a poor prognosis with an increased risk of cardiovascular (CV) events, including myocardial infarction (MI), stroke, limb ischemia and CV death; therefore, it is important to detect and treat PAD early. PAD and coronary artery disease (CAD) share a common pathogenesis and risk factors for development; therefore, cardiologists are in a unique position to screen, diagnosis and treat PAD. Moreover, PAD and CAD also share some treatment goals, including an aggressive modification of risk factors to reduce the risk of CV events. However, PAD remains an underdiagnosed and undertreated disease with medico-legal implications. As the role of cardiologists is expanding, the purpose of this review was to awaken the clinicians to the significance of PAD.

Antithrombotic Therapy in Peripheral Artery Disease: Current Evidence and Future Directions.

Patients with peripheral artery disease (PAD) are at an increased risk of major adverse cardiovascular events, and those with disease in the lower extremities are at risk of major adverse limb events primarily driven by atherothrombosis. Traditionally, PAD refers to diseases of the arteries outside of the coronary circulation, including carotid, visceral and lower extremity peripheral artery disease, and the heterogeneity of PAD patients is represented by different atherothrombotic pathophysiology, clinical features and related antithrombotic strategies. The risk in this diverse population includes systemic risk of cardiovascular events as well as risk related to the diseased territory (e.g., artery to artery embolic stroke for patients with carotid disease, lower extremity artery to artery embolism and atherothrombosis in patients with lower extremity disease). Moreover, until the last decade, clinical data on antithrombotic management of PAD patients have been drawn from subanalyses of randomized clinical trials addressing patients affected by coronary artery disease. The high prevalence and related poor prognosis in PAD patients highlight the pivotal role of tailored antithrombotic therapy in patients affected by cerebrovascular, aortic and lower extremity peripheral artery disease. Thus, the proper assessment of thrombotic and hemorrhagic risk in patients with PAD represents a key clinical challenge that must be met to permit the optimal antithrombotic prescription for the various clinical settings in daily practice. The aim of this updated review is to analyze different features of atherothrombotic disease as well as current evidence of antithrombotic management in asymptomatic and secondary prevention in PAD patients according to each arterial bed.

SIRT1 pharmacological activation rescues vascular dysfunction and prevents thrombosis in MTHFR deficiency.

Beyond well-assessed risk factors, cardiovascular events could be also associated with the presence of epigenetic and genetic alterations, such as the methylenetetrahydrofolate-reductase (MTHFR) C677T polymorphism. This gene variant is related to increased circulating levels of homocysteine (Hcy) and cardiovascular risk. However, heterozygous carriers have an augmented risk of cardiovascular accidents independently from normal Hcy levels, suggesting the presence of additional deregulated processes in MTHFR C677T carriers. Here, we hypothesize that targeting Sirtuin 1 (SIRT1) could be an alternative mechanism to control the cardiovascular risk associated to MTHFR deficiency condition. Flow Mediated Dilatation (FMD) and light transmission aggregometry assay were performed in subjects carrying MTHFR C677T allele after administration of resveratrol, the most powerful natural clinical usable compound that owns SIRT1 activating properties. MTHFR C677T carriers with normal Hcy levels revealed endothelial dysfunction and enhanced platelet aggregation associated with SIRT1 downregulation. SIRT1 activity stimulation by resveratrol intake was able to override these abnormalities without affecting Hcy levels. Impaired endothelial function, bleeding time, and wire-induced thrombus formation were rescued in a heterozygous Mthfr-deficient (Mthfr+/-) mouse model after resveratrol treatment. Using a cell-based high-throughput multiplexed screening (HTS) assay, a novel selective synthetic SIRT1 activator, namely ISIDE11, was identified. Ex vivo and in vivo treatment of Mthfr+/- mice with ISIDE11 rescues endothelial vasorelaxation and reduces wire-induced thrombus formation, effects that were abolished by SIRT1 inhibitor. Moreover, platelets from MTHFR C677T allele carriers treated with ISIDE11 showed normalization of their typical hyper-reactivity. These results candidate SIRT1 activation as a new therapeutic strategy to contain cardio and cerebrovascular events in MTHFR carriers.

Targeting the ASMase/S1P pathway protects from sortilin-evoked vascular damage in hypertension.

Sortilin has been positively correlated with vascular disorders in humans. No study has yet evaluated the possible direct effect of sortilin on vascular function. We used pharmacological and genetic approaches coupled with study of murine and human samples to unravel the mechanisms recruited by sortilin in the vascular system. Sortilin induced endothelial dysfunction of mesenteric arteries through NADPH oxidase 2 (NOX2) isoform activation, dysfunction that was prevented by knockdown of acid sphingomyelinase (ASMase) or sphingosine kinase 1. In vivo, recombinant sortilin administration induced arterial hypertension in WT mice. In contrast, genetic deletion of sphingosine-1-phosphate receptor 3 (S1P3) and gp91phox/NOX2 resulted in preservation of endothelial function and blood pressure homeostasis after 14 days of systemic sortilin administration. Translating these research findings into the clinical setting, we detected elevated sortilin levels in hypertensive patients with endothelial dysfunction. Furthermore, in a population-based cohort of 270 subjects, we showed increased plasma ASMase activity and increased plasma levels of sortilin, S1P, and soluble NOX2-derived peptide (sNOX2-dp) in hypertensive subjects, and the increase was more pronounced in hypertensive subjects with uncontrolled blood pressure. Our studies reveal what we believe is a previously unrecognized role of sortilin in the impairment of vascular function and in blood pressure homeostasis and suggest the potential of sortilin and its mediators as biomarkers for the prediction of vascular dysfunction and high blood pressure.

Venous Thromboembolism and Cancer: A Comprehensive Review from Pathophysiology to Novel Treatment.

Acute thrombotic events can unveil occult cancer, as they are its first manifestation in about 20 to 30% of all cases. Malignancy interacts in an intricate way with the hemostatic system, promoting both thrombosis and bleeding. The main pathway involved in these reactions involves the activation of tumor-associated procoagulant factors, which eventually results in clot formation. The clinical manifestation of cancer-related thrombotic events mainly involves the venous side, and manifests in a broad spectrum of conditions, including unusual sites of venous thrombosis. The selection of patients who have a balanced risk-benefit profile for management of anticoagulation is complex, given individual patient goals and preferences, different prognosis of specific cancers, common comorbidities, potential drug-drug interactions, underweight states, and the competing risks of morbidity and mortality. Anticoagulant treatment in cancer settings is broadly debated, considering the potential application of direct oral anticoagulants in both thromboprophylaxis and secondary prevention, having demonstrated its efficacy and safety compared to conventional treatment. This review aims to provide a brief overview of the pathophysiology and management of cancer-related thrombosis, summarizing the results obtained in recent clinical trials.

Conduction delays after transcatheter aortic valve implantation with balloon-expandable prosthesis and high implantation technique.

Performing transcatheter aortic valve implantation with high implantation technique, i.e. with an aorto-ventricular ratio > 60/40, reduces the need of permanent pacemaker implantation. Valve calcification and prosthesis oversizing are predictors of permanent pacemaker implantation, but there are no available data on their role when transcatheter aortic valve implantation is performed with an aorto-ventricular ratio > 60/40. The aim of this study was to evaluate the effect of leaflets/annulus calcification and prosthesis oversizing on the incidence of permanent pacemaker implantation after transcatheter aortic valve implantation with a high implantation technique. Transcatheter aortic valve implantation was performed in 48 patients implanting a balloon-expandable transcatheter heart valve with an aorto-ventricular ratio > 60/40. Calcium burden was assessed by preprocedural multidetector computed tomography. An invasive electrophysiological study was performed before and after transcatheter aortic valve implantation. Five patients (10.4%) needed permanent pacemaker implantation. At univariate analysis, baseline right bundle branch block and postprocedural PR, QRS and His-ventricular interval elongation significantly predicted permanent pacemaker implantation (p < 0.05). Receiver-operating characteristic curve analysis showed a correlation between transcatheter heart valve oversizing and permanent pacemaker implantation need, with the best cut-off being 17% (AUC = 0.72, p = 0.033). Linear regression analysis demonstrated that QRS complex elongation was related to total, left and non-coronary leaflet calcification (p < 0.05). This study demonstrates that, when transcatheter aortic valve implantation is performed using a balloon-expandable transcatheter heart valve deployed with an aorto-ventricular ratio > 60/40, the presence of leaflets/annulus calcification or the need to oversize the prosthesis correlate with the occurrence of pathological cardiac conduction delays.

Transverse aortic constriction induces gut barrier alterations, microbiota remodeling and systemic inflammation.

Accumulating evidence suggests that modifications of gut function and microbiota composition might play a pivotal role in the pathophysiology of several cardiovascular diseases, including heart failure (HF). In this study we systematically analysed gut microbiota composition, intestinal barrier integrity, intestinal and serum cytokines and serum endotoxin levels in C57BL/6 mice undergoing pressure overload by transverse aortic constriction (TAC) for 1 and 4 weeks. Compared to sham-operated animals, TAC induced prompt and strong weakening of intestinal barrier integrity, long-lasting decrease of colon anti-inflammatory cytokine levels, significant increases of serum levels of bacterial lipopolysaccharide and proinflammatory cytokines. TAC also exerted effects on microbiota composition, inducing significant differences in bacterial genera inside Actinobacteria, Firmicutes, Proteobacteria and TM7 phyla as shown by 16S rDNA sequencing of fecal samples from TAC or sham mice. These results suggest that gut modifications represent an important element to be considered in the development and progression of cardiac dysfunction in response to TAC and support this animal model as a valuable tool to establish the role and mechanisms of gut-heart crosstalk in HF. Evidence arising in this field might identify new treatment options targeting gut integrity and microbiota components to face adverse cardiac events.

Accuracy of global and regional longitudinal strain at peak of dobutamine stress echocardiography to detect significant coronary artery disease.

Dobutamine stress echocardiography (DSE) is sensitive but subjective diagnostic tool to detect inducible ischemia. Nowadays, speckle tracking allows an objective quantification of regional wall function. We aimed to investigate the feasibility and accuracy of global (GLS) and regional longitudinal strain (RLS) during DSE to detect significant coronary stenosis (SCS). We conducted a prospective observational multicenter study including patients undergoing DSE for suspected SCS. 50 patients with positive DSE underwent coronary angiography. Besides visual regional wall motion score index (WMSI), GLS and RLS were determined at rest and at peak stress by Automated Function Imaging. DSE GLS feasibility was 96%. Among 35 patients with SCS, 12 patients were affected by multivessel disease, 18 had stenosis of left anterior descending artery (LAD), 18 of left circumflex (LCX) and 15 of right coronary artery (RCA). At peak stress, both GLS reduction (p = 0.037) and WMSI worsening (p = 0.04) showed significant agreement with coronary angiography for detecting SCS. When single lesion was considered, peak stress GLS and LAD RLS were lower in the obstructed LAD regions than in normo-perfused territories (17.4 ± 5.5 vs. 20.5 ± 4.4%, p = 0.03; 17.1 ± 7.6 vs. 21.6 ± 5.5%, p < 0.02, respectively). Furthermore, the addition of RLS to regional WMSI was able to improve accuracy in LAD SCS prediction (AUC 0.68, p = 0.037). Conversely, in presence of LCX or RCA SCS, LS was less accurate than WMSI at peak stress. In conclusion, DSE strain analysis is feasible and may improve prediction of LAD SCS, whereas regional WMSI assessment performs better in presence of SCS of LCX and RCA.

Does left ventricular function predict cardiac outcome in Anderson-Fabry disease?

In Anderson-Fabry disease (AFD) the impact of left ventricular (LV) function on cardiac outcome is unknown. Noninvasive LV pressure-strain loop analysis is a new echocardiographic method to estimate myocardial work (MW). We aimed to evaluate whether LV function was associated with outcome and whether MW had a prognostic value in AFD. Ninety-six AFD patients (41.8 ± 14.7 years, 43.7% males) with normal LV ejection fraction were retrospectively evaluated. Inclusion criteria were sinus rhythm and ≥ 2-year follow-up. Standard echocardiography measurements, myocardial mechano-energetic efficiency (MEE) index, global longitudinal strain (GLS) and MW were evaluated. Adverse cardiac events were defined as composite of cardiac death, malignant ventricular tachycardia, atrial fibrillation and severe heart failure development. During a median follow-up of 63 months (interquartile range 37-85), 14 events occurred. Patient age, cardiac biomarkers, LV mass index, left atrium volume, E/Ea ratio, LV ejection fraction, MEE index, GLS and all MW indices were significantly related to adverse outcome at univariate analysis. After adjustment for clinical and echocardiographic parameters, which were significant at univariate analysis, GLS and MW resulted independent predictors of adverse events (p < 0.01). By ROC curve analysis, constructive MW ≤ 1513 mmHg% showed the highest sensitivity and specificity in predicting adverse outcome (92.9% and 86.6%, respectively). MW did not improve the predictive value of a model including clinical data, LV diastolic function and GLS. LV function impairment (both systolic and diastolic) is associated with adverse events in AFD. MW does not provide additive information over clinical features and systolic and diastolic function.

Focal reduction in left ventricular 123I-metaiodobenzylguanidine uptake and impairment in systolic function in patients with Anderson-Fabry disease.

BACKGROUND: Abnormalities of cardiac sympathetic innervation have been demonstrated in Anderson-Fabry disease (AFD). We aimed to investigate the relationship between regional left ventricular (LV) denervation and regional function abnormalities. METHODS: Twenty-four AFD patients (43.7 ± 12.8 years) were studied by 123I-metaiodobenzylguanidine (MIBG) cardiac imaging and speckle-tracking echocardiography. Segmental tracer uptake was estimated according to 0 to 4 score, and total defect score (TDS) was calculated for each patient. RESULTS: Segmental longitudinal strain worsened as MIBG uptake score increased (P < 0.001). By ROC analysis, a segmental longitudinal strain > - 16.2% predicted a segmental MIBG uptake score ≥1, with 79.7% sensitivity and 65.3% specificity. Segmental MIBG uptake defects were found in 13 out 24 AFD patients. LV mass index (60.8 ± 10.1 vs. 41.4 ± 9.8 g/h2.7), relative wall thickness (0.51 ± 0.06 vs. 0.40 ± 0.06), systolic pulmonary artery pressure (35.2 ± 6.7 vs. 27.2 ± 4.2 mmHg), and longitudinal strain (- 14.3 ± 2.7 vs. -19.4 ± 1.8%) were significantly higher in patients with segmental defect (all P < 0.01). At multivariate linear regression analysis, global longitudinal strain was independently associated with TDS (B = 3.007, 95% confidence interval 1.384 to 4.630, P = 0.001). CONCLUSIONS: Reduced cardiac MIBG uptake reflects the severity of cardiac involvement in AFD patients. LV longitudinal function impairment seems to be an earlier disease feature than regional myocardial denervation.

Impact of chronic kidney disease on platelet aggregation in patients with acute coronary syndrome.

AIMS: Chronic kidney disease (CKD) is associated with increased thrombotic events and seems to influence platelet reactivity. Conflicting results have been published on platelet response in CKD patients with stable coronary artery disease. The aim of our study was to investigate the impact of CKD on platelet aggregation in acute coronary syndrome (ACS) patients receiving dual antiplatelet therapy, included the more potent P2Y12 inhibitors. METHODS: We enrolled 206 patients with ACS, divided in two groups, according to the presence or the absence of moderate/severe CKD. Platelet aggregation was performed with light transmission aggregometry and results are expressed as percentage of maximum platelet aggregation. High residual platelet reactivity (HRPR) was defined as maximum platelet aggregation more than 59%. RESULTS: Patients with CKD [estimate glomerular filtration rate (eGFR) < 60 ml/min/1.73 m, n = 28] were prevalent older, diabetic, had previous coronary revascularization. In these patients, platelet aggregation was significantly higher than in those with eGFR ≥ 60 ml/min/1.73 m (ADP 10 µmol/l: 28.46 ±â€Š26.19 vs. 16.64 ±â€Š12.79, P < 0.001; ADP 20 µmol/l: 30.07 ±â€Š25.89 vs. 17.46 ±â€Š12.82, P < 0.001). HRPR was observed in 4.4% of patients, with higher prevalence in those with eGFR less than 60 ml/min/1.73 m [21.4 vs. 1.7%, P < 0.001, odds ratio (OR) [95% confidence interval (CI)] = 15.91 (3.71-68.17), P < 0.001]. At multivariate analysis, after correction for baseline confounders, eGFR [adjusted OR (95% CI) = 0.95 (0.91-0.98), P = 0.007], together with the use of clopidogrel [adjusted OR (95% CI) = 23.59 (4.01-138.82), P < 0.001], emerged as determinants of HRPR. CONCLUSION: In patients with ACS receiving dual antiplatelet therapy, CKD is associated with an increasing ADP-induced platelet aggregation and higher prevalence of HRPR, which is mainly correlated to clopidogrel use.

Left ventricular radial strain impairment precedes hypertrophy in Anderson-Fabry disease.

In Anderson-Fabry disease (AFD), left ventricular (LV) radial function has been scarcely investigated. We hypothesized that LV function may be affected by disease specific mechanisms and sought to comprehensively evaluate LV radial, circumferential and longitudinal function in a large population of AFD patients looking at the influence of LV geometry and fibrosis. We prospectively studied 94 consecutive AFD patients (41.5 ± 14.5 years; 41 men) with preserved LV ejection fraction (EF) utilizing speckle-tracking echocardiography. A subset of patients underwent gadolinium-enhanced cardiac magnetic resonance. Cases were compared to 48 healthy subjects matched for age and sex. LV concentric hypertrophy was found in 33 AFD patients while LV concentric remodeling (relative wall thickness ≥ 0.43) in 16 out 61 patients with normal LV mass. AFD patients had lower radial, longitudinal and circumferential strains than controls, independently by LV geometry pattern. Patients with LV hypertrophy showed reduced global longitudinal strain (p < 0.001) and early diastolic untwisting rate (p = 0.002) as compared to patients with normal geometry. In the whole AFD population, neither radial strain nor circumferential strain correlated with LV mass, while global longitudinal strain and early diastolic untwisting rate did (both p < 0.001). Late gadolinium enhancement was significantly associated with longitudinal strain, twisting rate and early diastolic untwisting rate, with twisting rate being the most powerful independent predictor (ß = - 0.461; p = 0.002). Findings demonstrate impairment of LV radial strain in AFD patients with preserved EF, even in a pre-hypertrophic stage. Development of LV hypertrophy and fibrosis make worse mostly longitudinal dysfunction.