ALEXANDRE LEMOS BORTOLOTTO
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
12 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 12
- Accelerated conversion of atrial fibrillation to normal sinus rhythm by pulmonary delivery of flecainide acetate in a porcine model(2018) VERRIER, Richard L.; BORTOLOTTO, Alexandre L.; SILVA, Bruna A.; MARUM, Alexandre A.; STOCCO, Fernando G.; EVARISTO, Ederson; ANTONIO, Victor Z. de; SILVA, Anderson C.; BELARDINELLI, LuizBACKGROUND Pulmonary delivery of antiarrhythmic agents has the potential to increase rapidly targeted drug concentrations in pulmonary veins and left atrium to terminate atrial fibrillation (AF). OBJECTIVE We evaluated the efficacy of flecainide administered via intratracheal instillation in terminating AF in a reliable preclinical model. METHODS In 11 closed-chest anesthetized Yorkshire pigs, AF was induced by intrapericardial administration of acetylcholine (1 mL of 102.5 mM solution) followed by burst pacing and allowed to continue for 2 minutes before intratracheal flecainide (0.4 or 0.75 mg/kg) administration. RESULTS Both the 0.4-and 0.75-mg/kg doses of intratracheal flecainide significantly reduced AF duration by 35% (P = .02) and 54% (P = .001), respectively, compared to no-drug baseline. There was a strong inverse correlation (r(2) = 0.87; P = .03) between the duration of AF and the change in atrial depolarization duration in response to intratracheal flecainide. Induction of AF resulted in a marked increase in ventricular rate and corresponding reduction in mean arterial pressure, which returned to baseline levels within 5 minutes after conversion. CONCLUSION Intratracheal flecainide instillation is effective in rapidly converting AF to normal sinus rhythm and restoring mean arterial pressure and heart rate to baseline values. The basis for this efficacy is likely rapid absorption of the drug through the lungs and delivery as a first-pass bolus to the left atrial and ventricular chambers and then to the coronary arterial circulation. The antiAF effect of flecainide is inversely correlated with the drug's prolongation of atrial depolarization, implicating slowing of intra-atrial conduction as an important mechanism underlying conversion of AF to normal sinus rhythm.
- Arterial stiffness and atrial fibrillation: A review(2022) LAGE, Joao Gabriel Batista; BORTOLOTTO, Alexandre Lemos; SCANAVACCA, Mauricio Ibrahim; BORTOLOTTO, Luiz Aparecido; DARRIEUX, Francisco Carlos da CostaArterial stiffness has been investigated as part of the physiopathology of arterial hypertension since the 1970s. Its role in increasing the ""pulsatile load"" imposed over the Left Ventricle (LV) has been intensely studied recently and has helped in understanding the mechanisms of Atrial Fibrillation (AF) in hypertensive patients. This paper aims to review the main evidence on this issue and establish possible mechanisms involved in the development of AF in patients with arterial stiffness. A PubMed search was performed, and selected articles were searched for references focusing on this topic. In the long term, lower blood pressure levels allow for arterial wall remodeling, leading to a lower stiffness index. To this day, however, there are no available treatments that directly promote the lowering of arterial wall stiffness. Most classes of anti-hypertensive drugs -with stronger evidence for betablockers and diuretics -could be effective in reducing arterial stiffness. There is strong evidence demonstrating an association between arterial stiffness and AF. New studies focusing on arterial stiffness and pre-fibrillatory stages would strengthen this causality relation.
conferenceObject Reversion of Severe Cardiac and Renal Dysfunction With Surgical Correction of Atypical Aortic Coarctation in Adult Patient: Case Report(2018) BORTOLOTTO, Alexandre L.; FILHO, Rogerio B.; MOREIRA, Everton L.; DALLAN, Luis A.; BORTOLOTTO, Luiz- ACUTE PULMONAR EDEMA AND VENTRICULAR DYSFUNCTION DUE ADRENERGIC MYOCARDITIS ASSOCIATED TO PHEOCHROMOCYTOMA(2019) BORTOLOTTO, Luiz Aparecido; BORTOLOTTO, Alexandre L.; CASTRO, Rafael; SOUSA, Maria T. S.; SOEIRO, Alexandre; PEREIRA, Adelaide
- Pulmonary Delivery of Metoprolol Reduces Ventricular Rate During Atrial Fibrillation and Accelerates Conversion to Sinus Rhythm(2020) MARUM, Alexandre A.; SILVA, Bruna Araujo; BORTOLOTTO, Alexandre L.; PEDREIRA, Giovanna C.; SILVA, Fernanda Tessarolo; MEDEIROS, Sofia A.; NEARING, Bruce D.; BELARDINELLI, Luiz; VERRIER, Richard L.Background: Safe, effective pulmonary delivery of cardioactive agents in humans is under development. Objectives: We examined whether intratracheal delivery of metoprolol can reduce ventricular rate during atrial fibrillation (AF) and accelerate conversion to sinus rhythm. Methods: In 7 closed-chest, anesthetized Yorkshire pigs, AF was induced by intrapericardial infusion of acetylcholine (1 mL of 102.5-mM solution) followed by atrial burst pacing and was allowed to continue for 2 minutes before intratracheal instillation of sterile water or metoprolol (0.2-mg/kg bolus) using a catheter positioned at the bifurcation of the main bronchi. High-resolution electrograms were obtained from catheters fluoroscopically positioned in the right atrium and left ventricle. Results: Rapid intratracheal instillation of metoprolol caused a 32-beat/min reduction in ventricular rate during AF (from 272 +/- 13.7 to 240 +/- 12.6 beats/min, P = 0.008) and a 2.3-minute reduction in AF duration (from 10.3 +/- 2.0 to 8.0 +/- 1.4 minutes, P = 0.018) compared with sterile water control. Conversion of AF to sinus rhythm was associated with rapid restoration (5-6 minutes) of heart rate and arterial blood pressure toward control values. Intratracheal metoprolol reduced AF dominant frequency by 31% (from 8.7 +/- 0.9 to 6.0 +/- 1.1 Hz, P = 0.04) compared with control and resulted in a trend toward a 5% increase in PR interval (from 174 +/- 11.2 to 182 +/- 11.4 ms, P = 0.07). Conclusions: Intratracheal delivery of metoprolol effectively reduces ventricular rate during AF and accelerates conversion to normal sinus rhythm in a pig model of acetylcholine-induced AF.
conferenceObject Targeting atrial depolarization (Pa) duration with pulmonary delivery of flecainide for rapid AF conversion(2018) VERRIER, R. L.; BORTOLOTTO, A. L.; SILVA, B. A.; MARUM, A.; STOCCO, F. G.; SILVA, A. C.; ANTONIO, V. Z. De; BELARDINELLI, A.- Regadenoson-induced T-wave heterogeneity complements coronary stenosis detection by myocardial perfusion imaging in men and women(2021) SILVA, Bruna Araujo; HAUSER, Thomas H.; NEARING, Bruce D.; BORTOLOTTO, Alexandre L.; MARUM, Alexandre A.; SILVA, Fernanda Tessarolo; MEDEIROS, Sofia A.; PEDREIRA, Giovanna C.; V, Ernest Gervino; VERRIER, Richard L.Aims We analysed whether incorporating electrocardiographic interlead T-wave heterogeneity (TWH) with myocardial perfusion imaging (MPI) during pharmacologic stress improves detection of flow-limiting lesions (FLL). Methods and results Medical records of all 103 patients at our institution who underwent stress testing with regadenoson (0.4 mg IV bolus) within 3 months of coronary angiography from September 2017 to March 2019 were studied. Cases (N = 59) had angiographically significant FLL (>= 50% of left main or >= 70% of other epicardial coronary arteries >= 2 mm in diameter); controls (N = 44) were normal or had non-FLL. TWH, i.e., interlead splay of T waves, was assessed from precordial leads V4-6 by second central moment analysis. Maximum TWHV(4-6 )levels during regadenoson stress were 68% higher in cases than in controls (P < 0.0001). TWHV4-6 generated areas under the receiver-operating characteristic (ROC) curve of 0.79 in men (P < 0.0001) and 0.71 in women (P = 0.007). In men, the ROC-guided 54-mu V TWHV4-6 cut-point for FLL produced adjusted odds of 7.3 [95% confidence interval (CI): 1.3-41.5, P = 0.03], 79% sensitivity, and 78% specificity. In women, the ROC-guided 35-mu V TWHV4-6 cut-point produced adjusted odds of 4.5 (95% CI: 1.1-18.9, P = 0.04), 84% sensitivity, and 52% specificity. Adding TWHV4-6 to MPI determinations reduced false-positive results by 70%, more than doubled true-negative results, and improved adjusted odds ratio to 6.8 (95% CI: 2.2-21.4, P = 0.001) with specificity of 78% in men and 86% in women. Conclusion This observational study is the first to demonstrate the benefit of combining TWHV4-6 with MPI to enhance FLL detection during MPI with regadenoson in both men and women.
- Preimplantation interlead ECG heterogeneity is superior to QRS complex duration in predicting mechanical super-response in patients with non-left bundle branch block receiving cardiac resynchronization therapy(2020) BORTOLOTTO, Alexandre L.; VERRIER, Richard L.; NEARING, Bruce D.; MARUM, Alexandre A.; SILVA, Bruna Araujo; PEDREIRA, Giovanna C.; SILVA, Fernanda Tessarolo; MEDEIROS, Sofia A.; SROUBEK, Jakub; ZIMETBAUM, Peter J.; CHANG, James D.BACKGROUND Reliable quantitative preimplantation predictors of response to cardiac resynchronization therapy (CRT) are needed. OBJECTIVE We tested the utility of preimplantation R-wave and T-wave heterogeneity (RWH and TWH, respectively) compared to standard QRS complex duration in identifying mechanical super-responders to CRT and mortality risk. METHODS We analyzed resting 12-lead electrocardiographic recordings from all 155 patients who received CRT devices between 2006 and 2018 at our institution and met class I and IIA American College of Cardiology/American Heart Association/Heart Rhythm Society guidelines with echocardiograms before and after implantation. Super-responders (n=35, 23%) had >= 20% increase in left ventricular ejection fraction and/or >= 20% decrease in left ventricular end-systolic diameter and were compared with non-super-responders (n=120, 77%), who did not meet these criteria. RWH and TWH were measured using second central moment analysis. RESULTS Among patients with non-left bundle branch block (LBBB), preimplantation RWH was significantly lower in super-responders than in non-super-responders in 3 of 4 lead sets ( P=.001 to P=.038) and TWH in 2 lead sets (both, P=.05), with the corresponding areas under the curve (RWH: 0.810-0.891, P<.001; TWH: 0.759-0.810, P <=.005). No differences were observed in the LBBB group. Preimplantation QRS complex duration also did not differ between super-responders and non-super-responders among patients with ( P=.856) or without ( P=.724) LBBB; the areas under the curve were nonsignificant (both, P=.69). RWH V1-3LILII >= 420 mu V predicted 3-year all-cause mortality in the entire cohort ( P=.037), with a hazard ratio of 7.440 (95% confidence interval 1.015-54.527; P=.048); QRS complex duration >= 150 ms did not predict mortality ( P=.27). CONCLUSION Preimplantation interlead electrocardiographic heterogeneity but not QRS complex duration predicts mechanical super-response to CRT in patients with non-LBBB.
- Multimodal mechanisms and enhanced efficiency of atrial fibrillation cardioversion by pulmonary delivery of a novel flecainide formulation(2020) SILVA, Fernanda Tessarolo; PEDREIRA, Giovanna C.; MEDEIROS, Sofia A.; BORTOLOTTO, Alexandre L.; SILVA, Bruna Araujo; HURREY, Michael; MADHAVAPEDDI, Prashanti; SCHULER, Carlos; BELARDINELLI, Luiz; VERRIER, Richard L.Introduction Inhaled flecainide significantly alters atrial electrical properties with the potential to terminate atrial fibrillation (AF) efficiently by optimizing dose and drug formulation. Methods Seventeen Yorkshire pigs were studied. Intrapericardial acetylcholine and burst pacing were used to induce AF. Effects of a novel cyclodextrin formulation (hydroxypropyl-ss-cyclodextrin [HP ss CD]) of flecainide (75 mg/mL, 0.5 or 1.0 mg/kg, bolus) instilled intratracheally at 2 minutes after AF initiation were studied. Concentration time-area analyses of flecainide HP ss CD were compared to the traditional acetate formulation. Results Intratracheal instillation of flecainide HP ss CD accelerated the conversion of AF to sinus rhythm in a dose-proportional manner, shortening AF duration by 47% (P = .014) and 79% (P = .002) at the lower and higher doses, respectively, compared to intratracheal sterile water placebo. AF dominant frequency was reduced by 11% (P = .04) and 29% (P = .004) respective to dose. At 2 minutes after intratracheal flecainide HP ss CD, atrial depolarization (P-a) duration increased by 12% (P = .02) and 17% (P = .009) at the lower and higher doses, respectively. At this time, the PR interval was prolonged by 9% (P = .04 for the higher dose) and AV node conduction was slowed, decreasing the ventricular rate during AF by 16% (P = .002) and 28% (P = .007) for the lower and higher doses. Flecainide HP ss CD achieved the more efficient conversion of AF than the acetate formulation, reflected in a markedly reduced area under the curve (P = .04). Conclusion Intratracheal instillation of the new flecainide HP ss CD formulation effectively terminates AF through efficient multimodal actions including slowing of atrial conduction velocity and decreasing AF dominant frequency, allowing reduced net drug delivery and inhalation time.
- STRESS-INDUCED T-WAVE HETEROGENEITY WITH REGADENOSON DETECTS CLINICALLY SIGNIFICANT CORONARY ARTERY STENOSIS(2019) SILVA, Bruna Araujo; NEARING, Bruce; BORTOLOTTO, Alexandre; MARUM, Alexandre; GERVINO, Ernest; VERRIER, Richard