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1.
Dis Markers ; 2020: 2696173, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32454903

RESUMO

Background: Few biomarkers are available for early identification of pulmonary arterial hypertension (PAH) and interstitial lung disease (ILD) in systemic sclerosis (SS) and scleroderma spectrum disorders (SSD). Aims: To evaluate Gas6, sAxl, and sMer as biomarkers for cardiopulmonary complications of SS and SSD. Methods: In a cross-sectional observational study, we recruited 125 consecutive patients, affected by SS and SSD and referred to a tertiary-level pulmonary hypertension outpatient clinic. All patients underwent a comprehensive evaluation for identification of PAH and ILD. Gas6, sMer, and sAxl concentrations were measured with ELISA protocols, and concentrations were compared according to PAH or ILD. Results: Nineteen subjects had pulmonary hypertension (PH) (14 PAH), and 39 had ILD (6 severe). Plasma sMer was increased in PAH (18.6 ng/ml IQR [11.7-20.3]) with respect to the absence (12.4 [8.0-15.8]) or other form of pulmonary hypertension (9.6 [7.4-12.5]; K-W variance p < 0.04). Conversely, Gas6 and sAxl levels were slightly increased in mild ILD (25.8 ng/ml [19.5-32.1] and 24.6 [20.1-32.5]) and reduced in severe ILD (16.6 [15.0-22.1] and 15.5 [14.9-22.4]) in comparison to no evidence of ILD (23.4 [18.8-28.1] and 21.6 [18.1-28.4]; K-W, p ≤ 0.05). Plasma sMer ≥ 19 ng/ml has 50% sensitivity and 92% specificity in PAH identification (area under the ROC curve (AUC) 0.697, p < 0.03). Values of Gas6 ≤ 24.5 ng/ml and of sAxl ≤ 15.5 ng/ml have 100% and 67% sensitivity and 47% and 86% specificity, respectively, in identifying severe ILD (Gas6 AUC 0.787, p < 0.001; sAxl AUC 0.705, p < 0.05). Conclusions: The assay of Gas6 sAxl and sMer may be useful to help in the identification of PAH and ILD in SS and SSD patients. The Gas6/TAM system seems to be relevant in cardiopulmonary complications of SS and SSD and merits further investigations.

2.
Biomarkers ; 25(2): 201-211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32063068

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

3.
Heart Fail Rev ; 25(1): 75-84, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31724111

RESUMO

Heart failure (HF) with either reduced or preserved ejection fraction is an increasingly prevalent condition. Cardiac imaging plays a central role in trying to identify the underlying cause of the underlying systolic and diastolic dysfunction, as the imaging findings have implications for patient's management and individualised treatment. The imaging modalities used more frequently in patients with heart failure in clinical routine are echocardiography and cardiac magnetic resonance. Both techniques keep some strengths and weakness due to their spatial and temporal resolution. Notably, several features in the diagnostic algorithm of heart failure with preserved systolic function (HFpEF) may be improved by an integrated approach. This review focuses on the role of each modality in characterising cardiac anatomy, systolic and diastolic function as well as myocardial tissue characterisation in the most common phenotypes of dilated and hypertrophied hearts.

5.
Clin Res Cardiol ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31748862

RESUMO

AIM: Aortic stenosis is a frequent valvular disease, with transcatheter aortic valve implantation (TAVI) being performed when surgical replacement is at increased risk. However, TAVI-induced effects on myocardial efficiency are unknown. We aimed to investigate changes in LV mechano-energetic pre-/post-TAVI and their prognostic impact. METHODS: A total of 46 patients (25 males) received transesophageal and simultaneous radial pressure plus transaortic gradient monitoring before/immediately after prosthesis deployment. Efficiency was computed as external work/potential energy, as derived from LV pressure-volume plots; myocardial oxygen consumption (MVO2) was estimated as PWImod, i.e. a noninvasively validated alternative for MVO2 estimation. RESULTS: TAVI was successful in all patients, peak transaortic gradient decreasing - 40 ± 20 mmHg (p < 0.001). Efficiency improved post-TAVI (+ 0.6 ± 0.12; p = 0.004), with a concomitant PWImod reduction (- 16 ± 31%; p < 0.001). When contextualized to fixed PWImod value (5 ml/min/100 g), efficiency significantly affected survival (p = 0.029). Over 1026 ± 450-day follow-up, a change in efficiency pre-/post-TAVI ≤ 0.021 (median of the difference) predicted more deaths from any cause (30%) as compared with a change > 0.021 (17%), particularly in those patients with a pre-TAVI mean high-gradient (HG ≥ 40 mmHg) phenotype (p < 0.05). In particular, HG patients exhibited the lowest efficiency/PWImod ratio pre-/post-TAVI (p = 0.048), relative to the other aortic stenosis patients, suggestive of an unfavourable matching between cardiac function and metabolic demand, which foreshortens some intrinsic damaged muscle condition in these patients. CONCLUSION: LV mechanical efficiency improves immediately post-TAVI, notwithstanding an inhomogeneous mechano-energetic matching among the aortic stenosis patients, which can impact negatively on their long-term prognosis, particularly in those with the HG phenotype.

6.
Dis Markers ; 2019: 4981982, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275447

RESUMO

Introduction/Objective: In the present paper, we aimed to test the value of the red cell distribution width (RDW) coefficient of variation as a candidate biomarker for pulmonary arterial hypertension (PAH) in patients with connective tissue disorders (CTD), correlating it with the degree of cardiopulmonary impairment in these patients. Methods: The study population included N = 141 patients with CTD and N = 59 patients affected by pulmonary hypertension of other etiologies, all referred to the Pulmonary Hypertension Clinic of the Cardiology Division of an Academic Hospital in Northern Italy for evaluation (including right catheterization). Clinical, instrumental, and laboratory data were collected and related to RDW and other full blood count indexes. Results: Twenty out of 141 CTD patients (14%) received a diagnosis of PAH. In comparison to those without PAH, CTD patients with PAH displayed a larger RDW (14.9% (13.5-17.2) vs. 13.8% (13.1-15.0); p = 0.02) and a lower platelet count (205 (177-240) × 109/l vs. 244 (197.5-304.2) × 109/l; p = 0.005). Moreover, with respect to CTD patients without PAH, RDW was significantly larger also in PH of other etiologies. In contrast, the platelet count was significantly lower only in CTD-related PAH, with a value > 276 × 109/l being 100% sensitive in ruling out PAH. Finally, RDW, but not the platelet count, was related directly to systolic pulmonary arterial pressure (r = 0.381; p = 0.0008) and right ventricle diameter (r = 0.283; p = 0.015) and inversely to diffusing capacity of the lung for carbon monoxide (r = -0.325; p = 0.014). Conclusion: RDW is a promising candidate biomarker for the screening and the prognostic stratification of PAH in CTD patients.


Assuntos
Doenças do Tecido Conjuntivo/complicações , Hipertensão Pulmonar/sangue , Idoso , Biomarcadores/sangue , Doenças do Tecido Conjuntivo/sangue , Contagem de Eritrócitos , Feminino , Humanos , Hipertensão Pulmonar/etiologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas
7.
J Cardiovasc Med (Hagerstown) ; 20(4): 169-179, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30829875

RESUMO

AIMS: Atrial fibrillation incidence is increasing due to ageing population and electrical cardioversion (ECV) is overused because of atrial fibrillation recurrences. Study's aim was to evaluate value of novel three-dimensional echocardiographic-derived left atrial conduit (LAC) function quantification in predicting early atrial fibrillation recurrence after ECV. METHODS: We included 106 patients [74 (64-78) years] who underwent ECV for persistent nonvalvular atrial fibrillation. For all clinical data and simultaneous left atrial and left ventricular (LV) three-dimensional full-volume data sets were available before ECV. We computed LAC as: [(LV maximum - LV minimum) - (left atrial maximum - left atrial minimum) volume], expressed as % LV stroke volume. Atrial fibrillation recurrence was checked with Holter monitoring. RESULTS: One month after ECV 66 patients were in sinus rhythm and 40 experienced atrial fibrillation recurrence. Pre-ECV patients with atrial fibrillation recurrence showed higher LAC contribution to LV filling (P < 0.0001) and noninvasively estimated left atrial stiffness (P < 0.0001) compared with sinus rhythm patients. There were no other differences, neither in clinical characteristics nor in LV properties. At multivariate LAC (P < 0.001), left atrial stiffness (P = 0.002) and volume (P = 0.043) predicted early atrial fibrillation relapse, even when compared with other confounding factors. Receiver-operating characteristics area (ROC) analysis confirmed LAC as best atrial fibrillation recurrence predictor (0.84, P < 0.0001), cut-off value more than 54% exhibiting reasonable sensibility-specificity (76-75%). CONCLUSION: Atrial fibrillation makes LV filling dependent on reciprocation between left atrial reservoir/conduit phases. Our data suggest that LAC larger contribution to filling in persistent atrial fibrillation patients reflects left atrial and LV diastolic dysfunction, which skews atrio-ventricular interaction that leads to atrial fibrillation perpetuation, making LAC a powerful atrial fibrillation recurrence predictor after ECV.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Função do Átrio Esquerdo , Ecocardiografia Tridimensional , Cardioversão Elétrica , Átrios do Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/diagnóstico por imagem , Função Ventricular Esquerda , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/fisiopatologia , Cardioversão Elétrica/efeitos adversos , Eletrocardiografia Ambulatorial , Feminino , Átrios do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Recidiva , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Disfunção Ventricular Esquerda/fisiopatologia
8.
Circ Cardiovasc Imaging ; 12(1): e008122, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-30632389

RESUMO

BACKGROUND: Assessment of left ventricular (LV) filling pressure is among the important components of a comprehensive echocardiographic report. Previous studies noted wide limits of agreement using 2009 American Society of Echocardiography/European Association of Echocardiography guidelines, but reproducibility of 2016 guidelines update in estimating LV filling pressure is unknown. METHODS: Echocardiographic and hemodynamic data were obtained from 50 patients undergoing cardiac catheterization for clinical indications. Clinical and echocardiographic findings but not invasive hemodynamics were provided to 4 groups of observers, including experienced echocardiographers and cardiology fellows. Invasively acquired LV filling pressure was the gold standard. RESULTS: In group I of 8 experienced echocardiographers from the guidelines writing committee, sensitivity for elevated LV filling pressure was 92% for all observers, and specificity was 93±6%. Fleiss κ-value for the agreement in group I was 0.80. In group II of 4 fellows in training, sensitivity was 91±2%, and specificity was 95±2%. Fleiss κ-value for the agreement in group II was 0.94. In group III of 9 experienced echocardiographers who had not participated in drafting the guidelines, sensitivity was 88±5%, and specificity was 91±7%. Fleiss κ-value for the agreement in group III was 0.76. In group IV of 7 other fellows, sensitivity was 91±3%, and specificity was 92±5%. Fleiss κ-value for the agreement in group IV was 0.89. CONCLUSIONS: There is a good level of agreement and accuracy in the estimation of LV filling pressure using the American Society of Echocardiography/European Association of Cardiovascular Imaging 2016 recommendations update, irrespective of the experience level of the observer.


Assuntos
Ecocardiografia Doppler/normas , Cardiopatias/diagnóstico por imagem , Ventrículos do Coração/diagnóstico por imagem , Guias de Prática Clínica como Assunto/normas , Função Ventricular Esquerda , Pressão Ventricular , Idoso , Feminino , Cardiopatias/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
9.
J Cardiol ; 73(3): 198-203, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30522897

RESUMO

BACKGROUND: ADP-antagonists such as prasugrel have reduced but yet not overcome the phenomenon of high-on treatment platelet reactivity (HRPR), that has been shown to increase the rate of major cardiovascular events after an acute coronary syndrome (ACS) or percutaneous coronary intervention (PCI). However, the exact prevalence and the principal determinants of suboptimal platelet inhibition in patients treated with dual antiplatelet therapy (DAPT) with prasugrel have not been completely clarified and were therefore the aim of the present study. METHODS: We included patients (<75 years and >60kg) treated with DAPT (aspirin+prasugrel) after PCI, mainly for an ACS. Platelet function test evaluation was performed at 1-3 months from discharge. HRPR was assessed by multiplate impedance aggregometry and defined for results above upper limit of normal after ADP stimulation. RESULTS: We included 190 post-ACS patients. HRPR with prasugrel was observed in 19 patients (10%). The prevalence of HRPR was stable in different high-risk subgroups of patients (female gender, hypercholesterolemic, and chronic kidney disease) whereas it was increased in diabetic patients (p=0.045), with a significant interaction between diabetic status and HRPR (p=0.04). However, at multivariate analysis, an impaired metabolic status, with higher levels of glycosylated hemoglobin and low-density lipoprotein (LDL) cholesterol, but not diabetic status, emerged as independent predictors of HRPR with prasugrel [OR (95% CI)=2.1 (1.32-3.33), p=0.002 and OR (95% CI)=1.03 (1.01-1.05), p=0.003, respectively], with a stronger linear relationship between ADP-mediated platelet aggregation and glycosylated hemoglobin levels (r=0.24, p=0.002), than for LDL-cholesterol (r=0.13, p=0.09). CONCLUSIONS: In post-ACS patients treated with PCI and receiving DAPT with prasugrel, HRPR is observed in about 10% of patients. Impaired metabolic status, and especially elevated glycosylated hemoglobin, emerged as independent predictors of the suboptimal effectiveness of prasugrel.


Assuntos
Síndrome Coronariana Aguda/terapia , Aspirina/efeitos adversos , Inibidores da Agregação de Plaquetas/efeitos adversos , Agregação Plaquetária/efeitos dos fármacos , Cloridrato de Prasugrel/efeitos adversos , Idoso , Aspirina/administração & dosagem , Plaquetas/efeitos dos fármacos , Terapia Antiplaquetária Dupla , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/métodos , Inibidores da Agregação de Plaquetas/administração & dosagem , Testes de Função Plaquetária , Período Pós-Operatório , Cloridrato de Prasugrel/administração & dosagem , Prevalência , Stents
10.
Circ J ; 83(2): 386-394, 2019 01 25.
Artigo em Inglês | MEDLINE | ID: mdl-30568053

RESUMO

BACKGROUND: Left ventricular (LV) torsion is an important aspect of cardiac mechanics and is altered in heart failure patients. Cardiac resynchronization therapy (CRT) has a positive effect on LV function, but the exact mechanisms through which it works are not completely depicted. Our aim was to investigate (1) the acute CRT effect on LV torsional mechanics in heart failure patients using 3D speckle tracking echocardiography (3DSTE) and (2) its effect on short-term LV remodeling. Methods and Results: We considered 48 patients (age 72±11 years, 35 men) who received CRT. They underwent 3DSTE during CRT-on (biventricular stimulation) vs. CRT-off (intrinsic conduction/right atrial/ventricular stimulation alone), in a random fashion. Patients were classified as CRT responders based on LV systolic volume reduction ≥15% at 6 months (final population: 31 responders, 17 non-responders). Acute CRT positively affected responders in terms of LV torsion (from 0.32±0.06°/cm CRT-off to 0.41±0.06°/cm CRT-on), but adversely affected non-responders (from 0.54±0.08°/cm CRT-off to 0.28±0.08°/cm CRT-on, interaction P=0.02). A similar trend was confirmed for apical (interaction P<0.04), but not for basal torsion (interaction P=0.351). CONCLUSIONS: CRT has a positive role in acute recovery of LV torsion (particularly in its apical component) in responders, likely modulating the improvement in LV remodeling at early follow-up.


Assuntos
Terapia de Ressincronização Cardíaca/métodos , Disfunção Ventricular Esquerda/terapia , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia Tridimensional/métodos , Feminino , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Volume Sistólico , Sístole , Resultado do Tratamento , Função Ventricular Esquerda
11.
J Am Soc Echocardiogr ; 31(12): 1272-1284.e9, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30146187

RESUMO

BACKGROUND: Stress testing helps diagnose heart failure with preserved ejection fraction (HFpEF), but there are no established criteria for quantifying left ventricular (LV) functional reserve. The aim of this study was to investigate whether comprehensive analysis of the timing and amplitude of LV long-axis myocardial motion and deformation throughout the cardiac cycle during rest and stress can provide more informative criteria than standard measurements. METHODS: Velocity, strain, and strain rate traces were measured from all 18 LV segments by echocardiographic myocardial velocity imaging at rest and during semisupine bicycle exercise in 100 subjects aged 69 ± 7 years, including patients with HFpEF and healthy, hypertensive, and breathless control subjects. A machine-learning algorithm, composed of an unsupervised statistical method and a supervised classifier, was used to model spatiotemporal patterns of the traces and compare the predicted labels with the clinical diagnoses. RESULTS: The learned strain rate parameters gave the highest accuracy for allocating subjects into the four groups (overall, 57%; for patients with HFpEF, 81%), and into two classes (asymptomatic vs symptomatic; area under the curve, 0.89; accuracy, 85%; sensitivity, 86%; specificity, 82%). Machine learning of strain rate, compared with standard measurements, gave the greatest improvement in accuracy for the two-class task (+23%, P < .0001), compared with +11% (P < .0001) using velocity and +4% (P < .05) using strain. Strain rate was also best at predicting 6-min walk distance as an independent reference criterion. CONCLUSIONS: Machine learning of spatiotemporal variations of LV strain rate during rest and exercise could be used to identify patients with HFpEF and to provide an objective basis for diagnostic classification.


Assuntos
Ecocardiografia/métodos , Insuficiência Cardíaca/diagnóstico , Ventrículos do Coração/diagnóstico por imagem , Aprendizado de Máquina , Contração Miocárdica/fisiologia , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Idoso , Teste de Esforço , Tolerância ao Exercício/fisiologia , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Humanos , Masculino , Estudos Prospectivos
13.
J Invasive Cardiol ; 30(4): 133-137, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29610443

RESUMO

BACKGROUND: Long coronary lesions still remain a challenge, with poor immediate results and suboptimal outcomes when compared to class A/B1 lesions. The presence of overlapped segments of metal struts and polymer might trigger an abnormal inflammatory reaction, resulting in a higher restenosis rate. The aim of our study was to evaluate the safety, feasibility, and cost effectiveness of a 48 mm everolimus-eluting stent (EES) during treatment of very long coronary lesions. METHODS AND RESULTS: The FREIUS study is a prospective data collection of consecutive patients undergoing 48 mm EES implantation in six high-volume European centers. Each patient was matched through a propensity score to a comparable patient treated with two or more second-generation overlapped drug-eluting stents. The primary endpoint was the combined incidence of cardiac death, target-vessel myocardial infarction, and target-lesion revascularization (device-oriented composite endpoint [DOCE]). The secondary endpoints were all-cause death, each individual component of the primary endpoint, and definite/probable stent thrombosis. From January 2014 to April 2015, a total of 218 patients were treated with at least one 48 mm EES and were compared with 218 matched controls. Overall, 9% of patients reached the primary endpoint. Cumulative survival free from DOCE incidence did not differ between the two groups (7% in the cases vs 10.5% in the controls; P=.10). After multivariable analysis, only clinical presentation with myocardial infarction (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.5-2.1; P=.01) and stent number (HR, 1.4; 95% CI, 1.1-1.8; P=.02) emerged as independent predictors of DOCE. CONCLUSION: The use of 48 mm EES offers a safe and effective strategy for the treatment of very long coronary lesions.


Assuntos
Trombose Coronária/cirurgia , Stents Farmacológicos , Everolimo/farmacologia , Intervenção Coronária Percutânea/métodos , Pontuação de Propensão , Idoso , Angiografia Coronária , Trombose Coronária/diagnóstico , Trombose Coronária/mortalidade , Europa (Continente)/epidemiologia , Feminino , Humanos , Masculino , Estudos Prospectivos , Desenho de Prótese , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento
14.
Pacing Clin Electrophysiol ; 41(6): 597-602, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29635696

RESUMO

BACKGROUND: Simultaneous cathodic-anodal capture by a bipole of a cardiac resynchronization therapy (CRT) left-ventricular (LV) catheter may depolarize a larger LV area than conventional multipoint pacing. We evaluated the feasibility of cathodic-anodal LV stimulation. METHODS: In 30 patients undergoing CRT with a quadripolar LV lead, we evaluated the cathodic and anodal capture threshold for each LV pole and compared QRS on electrocardiogram (ECG) during single-point cathodic biventricular stimulation (S-BS), multipoint BS (M-BS), and cathodic-anodal BS (CA-BS). RESULTS: Anodal capture was obtained by three poles in 23/30 patients, by two poles in five, and was not feasible in two. The mean single-point anodal threshold was 3.93 V versus single-point cathodic threshold of 1.95 V. On comparing ECGs, M-BS and CA-BS produced similar QRS wavefront activation in 90% of patients. CONCLUSIONS: CA-BS is feasible and may be used in LV pacing to achieve a different wavefront of electrical activation. Further prospective studies are needed in order to verify the clinical impact of this kind of stimulation.


Assuntos
Bloqueio de Ramo/fisiopatologia , Bloqueio de Ramo/terapia , Dispositivos de Terapia de Ressincronização Cardíaca , Terapia de Ressincronização Cardíaca/métodos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Ventrículos do Coração/fisiopatologia , Idoso , Eletrocardiografia , Estudos de Viabilidade , Feminino , Humanos , Masculino , Resultado do Tratamento
15.
Circ Cardiovasc Imaging ; 11(4): e007138, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29661795

RESUMO

BACKGROUND: Current diagnosis of heart failure with preserved ejection fraction (HFpEF) is suboptimal. We tested the hypothesis that comprehensive machine learning (ML) of left ventricular function at rest and exercise objectively captures differences between HFpEF and healthy subjects. METHODS AND RESULTS: One hundred fifty-six subjects aged >60 years (72 HFpEF+33 healthy for the initial analyses; 24 hypertensive+27 breathless for independent evaluation) underwent stress echocardiography, in the MEDIA study (Metabolic Road to Diastolic Heart Failure). Left ventricular long-axis myocardial velocity patterns were analyzed using an unsupervised ML algorithm that orders subjects according to their similarity, allowing exploration of the main trends in velocity patterns. ML identified a continuum from health to disease, including a transition zone associated to an uncertain diagnosis. Clinical validation was performed (1) to characterize the main trends in the patterns for each zone, which corresponded to known characteristics and new features of HFpEF; the ML-diagnostic zones differed for age, body mass index, 6-minute walk distance, B-type natriuretic peptide, and left ventricular mass index (P<0.05) and (2) to evaluate the consistency of the proposed groupings against diagnosis by current clinical criteria; correlation with diagnosis was good (κ, 72.6%; 95% confidence interval, 58.1-87.0); ML identified 6% of healthy controls as HFpEF. Blinded reinterpretation of imaging from subjects with discordant clinical and ML diagnoses revealed abnormalities not included in diagnostic criteria. The algorithm was applied independently to another 51 subjects, classifying 33% of hypertensive and 67% of breathless controls as mild-HFpEF. CONCLUSIONS: The analysis of left ventricular long-axis function on exercise by interpretable ML may improve the diagnosis and understanding of HFpEF.


Assuntos
Ecocardiografia sob Estresse , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/fisiopatologia , Aprendizado de Máquina , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Idoso , Algoritmos , Teste de Esforço , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Descanso , Volume Sistólico
16.
Pharmacol Res ; 129: 27-33, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29355684

RESUMO

Dual antiplatelet therapy constitutes a key point in the management of patients with acute coronary syndromes. In particular, ticagrelor, an ADP-antagonist, can provide a more potent and predictable platelet inhibition as compared to clopidogrel, and adenosine-mediated pathways have been involved in its beneficial effects on mortality and myocardial perfusion. However, a quote of patients still displays a suboptimal platelet inhibition on ticagrelor, and, while the role of genetics in conditioning clopidogrel resistance is well established, few data have been reported for ticagrelor. We investigated the impact of rs5751876 C > T polymorphism of adenosine A2a receptor (ADORA2a) on platelet reactivity in patients during chronic treatment with ticagrelor. We included patients treated with ASA and ticagrelor for a recent ACS or elective coronary revascularization. Platelet reactivity was assessed at 30-90 days post-discharge by multiple-electrode aggregometry. HRPR for ticagrelor was defined as ADP-test results >417 AU*min. Genetic analysis was performed to assess the presence of rs5751876 C > T polymorphism of ADORA2a receptor. We included 244 patients in our study, 174 (71.3%) patients carried the polymorphism (T allele), 51 (20.9%) of them in homozygosis (T/T). C-allele carriers (homozygotes C/C and heterozygotes C/T) showed no difference in baseline characteristics but for lower HDL-cholesterol (p = 0.01). An absolute lower rate of HRPR on ticagrelor was observed in homozygotes T/T (p = 0.03). At multivariate analysis, C allele carriage was independently associated with the rate of HRPR on ticagrelor (adjusted OR[95%CI] = 4.63[1.02-21.01], p = 0.048). Our study results showed a significant independent association between rs5751876 allele C carriage and a higher rate of high residual platelet reactivity in patients on ticagrelor after a recent ACS or PCI.


Assuntos
Síndrome Coronariana Aguda/tratamento farmacológico , Inibidores da Agregação de Plaquetas/uso terapêutico , Agregação Plaquetária/efeitos dos fármacos , Receptor A2A de Adenosina/genética , Ticagrelor/uso terapêutico , Síndrome Coronariana Aguda/genética , Idoso , Aspirina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Polimorfismo Genético
17.
Clin Res Cardiol ; 107(4): 329-337, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29181725

RESUMO

BACKGROUND: Diastolic dysfunction promotes atrial fibrillation (AF) inducing left atrial (LA) remodeling, with chamber dilation and fibrosis. Predominance of LA phasic conduit (LAC) function should reflect not only chamber alterations but also underlying left ventricular (LV) filling impairment. Thus, LAC was tested as possible predictor of early AF relapse after electrical cardioversion (EC). METHODS: 96 consecutive patients, who underwent EC for persistent non-valvular AF, were prospectively enrolled. Immediately after successful EC (3 h ± 15 min), an echocardiographic apical four-chamber view was acquired with transmitral velocities, annular tissue Doppler and simultaneous LV and LA three-dimensional full-volume datasets. Then, from LA-LV volumetric curves we computed LAC as: [(LV maximum - LV minimum) - (LA maximum - LA minimum) volume], expressed as % LV stroke volume. LA pump, immediately post-EC, was assumed and verified as being negligible. Sinus rhythm persistence at 1 month was checked with ECG-Holter monitoring. RESULTS: At 1 month 62 patients were in sinus rhythm and 34 in AF. AF patients presented pre-EC higher E/é values (p = 0.012), no major LA volume differences (p = NS), but a stiffer LV cavity (p = 0.012) for a comparable LV capacitance (p = 0.461). Conduit contributed more (p < 0.001) to LV stroke volume in AF subpopulation. Multiple regression revealed LAC as the most significant AF predictor (p = 0.013), even after correction for biometric characteristics and pharmacotherapy (p = 0.008). CONCLUSION: Our data suggest that LAC larger contribution to LV filling soon after EC reflects LA-LV stiffening, which skews atrioventricular interaction leading to AF perpetuation and makes conduit dominance a powerful predictor of early AF recurrence.


Assuntos
Fibrilação Atrial/terapia , Função do Átrio Esquerdo , Remodelamento Atrial , Cardioversão Elétrica/efeitos adversos , Função Ventricular Esquerda , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Ecocardiografia Doppler , Eletrocardiografia Ambulatorial , Feminino , Humanos , Masculino , Estudos Prospectivos , Recidiva , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento
18.
Angiology ; 69(6): 490-496, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29082748

RESUMO

The immature platelet count (IPC) is a potential marker of platelet reactivity. We assessed the relationship between IPC during chronic dual antiplatelet therapy (DAPT) and the response to antiplatelet drugs (acetylsalycilic acid + clopidogrel/ticagrelor). We included 286 patients: 167 (58.4%) patients received ticagrelor and 119 (41.6%) received clopidogrel. At a median follow-up of 46.5 days, the variation in IPC displayed an absolute median (interquartile range [IQR]) of -11.9 × 103/µL (-182.7 to 160.8), corresponding to a median percentage change in IPC ([%ΔIPC] IQR) of -0.3% (-21.9% to 35.5%), with an increase in IPC levels in those on ticagrelor and a decrease in IPC levels in those on clopidogrel. We observed an inverse association of lower platelet reactivity at different tests and a higher increase in IPC ( r = -0.14, P = .04 for arachidonic acid test; r = -0.12, P = .05 for collagen test; and r = -0.13, P = .02 for adenosine diphosphate test [ADP]). The rate of poor effectiveness of ADP antagonists was the only independent predictor of a ΔIPC above the third tertile (odds ratio [95% confidence interval] = 0.55 [0.32-0.99]; P = .048). We showed that in patients treated with chronic DAPT, an increase in IPC is significantly related to lower levels of platelet reactivity.


Assuntos
Síndrome Coronariana Aguda/sangue , Doença da Artéria Coronariana/sangue , Ativação Plaquetária , Inibidores da Agregação de Plaquetas/administração & dosagem , Contagem de Plaquetas , Síndrome Coronariana Aguda/terapia , Idoso , Aspirina/administração & dosagem , Clopidogrel/administração & dosagem , Doença da Artéria Coronariana/terapia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Ticagrelor/administração & dosagem
19.
Coron Artery Dis ; 29(2): 138-144, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29028737

RESUMO

BACKGROUND: Fractional flow reserve (FFR) currently represents the gold standard in the evaluation of the haemodynamic relevance of coronary stenoses. However, both intracoronary and intravenous adenosine may be tolerated poorly by some patients. Therefore, considerable interest had been focused in the last few years on new adenosine-free indexes to define the haemodynamic relevance of coronary stenoses. So far, few data have been reported on resting Pd/Pa and its correlation with FFR as evaluated with high-dose intracoronary adenosine administration, which is the aim of the current study. MATERIALS AND METHODS: FFR was assessed in 120 patients with 137 intermediate lesions during cardiac catheterization by a pressure-recording guidewire (PrimeWire). FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperaemia. Intracoronary doses of adenosine were administered up to 720 µg as intracoronary boli. Exclusion criteria were as follows: (a) allergy to adenosine; (b) baseline bradycardia (heart rate <50 bpm); (c) hypotension (blood pressure <90 mmHg); and (d) refusal to provide signed informed consent. RESULTS: High doses of intracoronary adenosine were well tolerated, with no major side effects. Increasing doses up to 720 µg progressively decreased FFR values and increased the percentage of patients showing an FFR less than 0.80. Resting Pd/Pa showed good accuracy in the identification of patients with significant FFR values (<0.80) [area under the curve=0.9 (0.84-0.96), P<0.0001]. Using receiver-operating characteristic curves, we identified a threshold less than 0.93 as the best accurate cut-off value in the prediction of a positive FFR value. A value up to 0.88 was associated with a 100% positive predictive value, whereas a value of at least 0.95 was associated with a 95% negative predictive value. CONCLUSION: This study showed that in intermediate lesions, resting Pd/Pa was related linearly to FFR. We identified 0.93 as the best cut-off value in the prediction of haemodynamically significant coronary stenosis as evaluated by FFR. However, cut-off values of 0.88 and 0.95 could provide the maximal predictive positive and negative values, suggesting the additional use of FFR only in patients with resting values within this range.


Assuntos
Cateterismo Cardíaco , Estenose Coronária/diagnóstico , Vasos Coronários/fisiopatologia , Reserva Fracionada de Fluxo Miocárdico , Hemodinâmica , Adenosina/administração & dosagem , Idoso , Angiografia Coronária , Estenose Coronária/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Reprodutibilidade dos Testes , Vasodilatadores/administração & dosagem
20.
Indian Pacing Electrophysiol J ; 17(2): 29-33, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29072989

RESUMO

BACKGROUND: Indication to implantable cardioverter defibrillator (ICD) for primary prevention of sudden death relies on left ventricular ejection fraction (LVEF). We measured the proportion of patients in whom indication to ICD persisted at the time of generator replacement (GR) and searched for predictors of appropriate therapies after GR. METHODS: We identified all consecutive patients who had received an ICD at our hospital, for LVEF ≤35% and no previous arrhythmias or unexplained syncope. Then, we included the 166 patients who outlived their first device and underwent GR. RESULTS: At the time of GR (mean follow-up 59 ± 20 months), ICD indication (i.e. LVEF ≤35% or previously treated ventricular arrhythmias) persisted in 114 (69%) patients. After GR, appropriate ICD therapies were delivered in 30 (26%) patients with persistent ICD indication and in 12 (23%) of the remaining patients (p = 0.656). Nonetheless, the annual rate of therapies was higher in the first group (1.08 versus 0.53 events/year; p < 0.001), as well as the rate of inappropriate therapies (0.03 versus 0 events/year; p = 0.031). The only independent predictor of appropriate ICD therapies after GR was the rate of shocks received before replacement (Hazard Ratio: 1.41; 95% confidence interval: 1.01-1.96; p = 0.041). CONCLUSION: In heart failure with reduced LVEF, ICD indication persisted at the time of GR in 69% of patients. However, even in the absence of persistent ICD indication at GR, the risk of recurrence of arrhythmic events was not null.

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