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Hyperglycaemia is common during acute coronary syndromes (ACS) irrespective of diabetic status and portends excess infarct size and mortality, but the mechanisms underlying this effect are poorly understood. We hypothesized that sodium/glucose linked transporter-1 (SGLT1) might contribute to the effect of high-glucose during ACS and examined this using an ex-vivo rodent heart model of ischaemia-reperfusion injury. Langendorff-perfused rat hearts were subjected to 35 min ischemia and 2 h reperfusion, with variable glucose and reciprocal mannitol given during reperfusion in the presence of pharmacological inhibitors of SGLT1. Myocardial SGLT1 expression was determined in rat by rtPCR, RNAscope and immunohistochemistry, as well as in human by single-cell transcriptomic analysis. High glucose in non-diabetic rat heart exacerbated reperfusion injury, significantly increasing infarct size from 45 ± 3 to 65 ± 4% at 11-22 mmol/L glucose, respectively (p < 0.01), an association absent in diabetic heart (32 ± 1-37 ± 5%, p = NS). Rat heart expressed SGLT1 RNA and protein in vascular endothelium and cardiomyocytes, with similar expression found in human myocardium by single-nucleus RNA-sequencing. Rat SGLT1 expression was significantly reduced in diabetic versus non-diabetic heart (0.608 ± 0.08 compared with 1.116 ± 0.13 probe/nuclei, p < 0.01). Pharmacological inhibitors phlorizin, canagliflozin or mizagliflozoin in non-diabetic heart revealed that blockade of SGLT1 but not SGLT2, abrogated glucose-mediated excess reperfusion injury. Elevated glucose is injurious to the rat heart during reperfusion, exacerbating myocardial infarction in non-diabetic heart, whereas the diabetic heart is resistant to raised glucose, a finding which may be explained by lower myocardial SGLT1 expression. SGLT1 is expressed in vascular endothelium and cardiomyocytes and inhibiting SGLT1 abrogates excess glucose-mediated infarction. These data highlight SGLT1 as a potential clinical translational target to improve morbidity/mortality outcomes in hyperglycemic ACS patients.
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OBJECTIVE: To investigate the utility of simultaneous multi-catheter cryotherapy for the treatment of APs that were previously resistant to standard radiofrequency (RF) catheter ablation. BACKGROUND: Catheter ablation is established in the treatment of accessory pathways (AP), with high rates of permanent procedural success with a single attempt. However, there are still instances of acute procedural failure and AP recurrences with standard RF and cryotherapy methods. METHODS: Seven consecutive cases of pre-excitation syndromes with prior failed RF catheter ablation had the novel treatment. Cryotherapy was delivered using two 8 mm tip focal cryoablation catheters (Freezor® Max, Medtronic, Minneapolis, Minnesota, USA). RESULTS: Accessory pathway localisation was septal in 5 cases, left posterolateral in 1, right lateral in 1. In all cases, ablation of the AP was acutely successful with no procedural complications. Median procedure and fluoroscopy durations were 199 and 35 min, sequentially. Median Procedure duration fell significantly in the second half of series (174 min) compared to the first half (233 min, P = 0.05). One patient had evidence of a recurring AP conduction with pre-excitation at 5-week follow up. After a median follow up of 66.8+-6.5 months, 6 out of 7 patients remained asymptomatic and free of pre-excitation. CONCLUSION: Simultaneous multi-catheter cryotherapy is feasible, safe and can provide definitive cure of accessory pathways that were previously resistant to standard radiofrequency ablation. Further study is required in the assessment of this novel form of advanced cryotherapy to treat complex and resistant arrhythmias.
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AIMS: To investigate the abnormalities of the coronary venous system in candidates for cardiac resynchronization therapy (CRT) and describe methods for circumventing the resulting difficulties. METHODS: From four implanting institutes, data of all CRT implants between October 2008 and October 2020 were screened for abnormal cardiac venous anatomy, defined as an anatomical variation not conforming to the accepted 'normal' anatomy. Patient demographics, procedural detail, and subsequent left ventricle (LV) lead pacing indices were collected. RESULTS: From a total of 3548 CRT implants, 15 (0.42%) patients (80% male) of 72.2 ± 10.6 years in age with an LV ejection fraction of 34 ± 10.3% were identified to have had an abnormal cardiac venous anatomy over the study period. There were 13 cases of persistent left side superior vena cava (pLSVC), five of which had coronary sinus ostium atresia (CSOA) including two with an "unroofed" coronary sinus (CS); one patient had a unique anomalous origin of the CS and one patient had an isolated CSOA. In total 14 patients (60% repeat attempt) had successful percutaneous implant under general anesthesia (46.7%) via the cephalic vein (59.1%), using the femoral approach (53.3%) for levophase venography and/or pull-through, including one case of endocardial LV implant. Pacing follow-up over 37.64 ± 37.6 months demonstrated LV lead threshold between 0.62 and 2.9 volts (pulsewidth 0.4-1.5 ms) in all cases; five patients died within 2.92 ± 1.6 years of a successful implant. CONCLUSION: CRT devices can be implanted percutaneously even in the presence of substantial abnormalities of coronary venous anatomy. Alternative routes of venous access may be required.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Veia Cava Superior Esquerda Persistente , Malformações Vasculares , Terapia de Ressincronização Cardíaca/métodos , Dispositivos de Terapia de Ressincronização Cardíaca , Drenagem , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Masculino , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagemRESUMO
INTRODUCTION: Generic ICD programming, where shock-reduction programming is extrapolated from trials of one manufacturer to another, may reduce non-essential ICD therapies beyond that seen in randomized trials. However, the benefits and risks are unknown. The purpose of this retrospective cohort study was to evaluate the impact of a standardized programming protocol, based on generic programming, across manufacturers. METHODS: We included all new ICDs in a single center (2009-2019). In 2013 a standardized programming protocol based on generic programming was introduced, incorporating high detection rates (200 bpm for primary prevention) and long detection (30/40 or equivalent in VF zone) for all patients. Patients were classified into three groups based on implant programming: pre-guideline (PS), post-guideline and guideline compliant (GC) and post-guideline but not guideline compliant (NGC). The end-points were the first occurrence of any device therapy (ATP or shock), ICD shock, syncope and all-cause mortality. Survival analysis was used to evaluate outcomes. RESULTS: 1003 patients were included (mean follow-up 1519 ± 1005 days). In primary prevention patients (n = 583) freedom from ICD therapy (91.5% vs. 73.6%, p < .001) or shock (94.7% vs 84.8%, p = .02) were significantly higher in GC compared to PS patients, without significant increase in syncope or mortality. In secondary prevention patients (n = 420) freedom from any ICD therapy or any shock were non-significantly higher in GC compared to PS patients, without an increase in syncope or mortality. CONCLUSIONS: In primary prevention patients a standardized programming protocol, incorporating generic programming, reduced the burden of ICD therapy without an increase in adverse outcomes.
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Algoritmos , Desfibriladores Implantáveis/normas , Desenho de Prótese , Idoso , Feminino , Fidelidade a Diretrizes , Humanos , Masculino , Pessoa de Meia-Idade , Prevenção Primária , Estudos Retrospectivos , Prevenção SecundáriaRESUMO
BACKGROUND: Cardiac resynchronization therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter-defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. METHODS: Data was collected from three CRT-D implanting centers between October 2008 and September 2017. In total 633 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of "cephalic" (ICD lead via cephalic) versus "non-cephalic" (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. RESULTS: The cephalic and non-cephalic cohorts were equally male (81.9% vs. 78%; p = .26), similar in age (69.7 ± 11.5 vs. 68.7 ± 11.9; p = .33) and body mass index (BMI) (27.7 ± 5.1 vs. 27.1 ± 5.7; p = .33). Most ICD leads were implanted via the cephalic vein (73.5%) and patients had a mean of 2.9 ± 0.28 leads implanted via this route. The rate of ICD lead failure was low and statistically similar between both groups (0.36%/year vs. 0.13%/year; p = .12). Female gender was more common in the lead failure cohort than non-failure (55.6% vs. 17.9%, respectively; p = .004) as was hypertension (88.9% vs. 54.2%, respectively, p = .038). On multivariate Cox-regression, female sex (p = .008; HR, 7.12 [1.7-30.2]), and BMI (p = .047; HR, 1.12 [1.001-1.24]) were significantly associated with ICD lead failure. CONCLUSION: CRT-D implantation via the cephalic route is not significantly associated with premature ICD lead failure. Female gender and BMI are predictors of lead failure.
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Hipertensão , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Masculino , Resultado do TratamentoAssuntos
Arritmias Cardíacas/diagnóstico , COVID-19/prevenção & controle , Controle de Infecções , Telemedicina , Telemetria , Potenciais de Ação , Arritmias Cardíacas/fisiopatologia , COVID-19/transmissão , Frequência Cardíaca , Humanos , Londres , Valor Preditivo dos Testes , Telemedicina/instrumentação , Telemetria/instrumentaçãoRESUMO
AIMS: Restoring sinus rhythm (SR) by ablation alone is an endpoint used in radiofrequency (RF) ablation for long-standing persistent atrial fibrillation (AF) but not with cryotherapy. The simultaneous use of two cryotherapy catheters can improve ablation efficiency; we compared this with RF ablation in chronic persistent AF aiming for termination to SR by ablation alone. METHODS AND RESULTS: Consecutive patients undergoing their first ablation for persistent AF of >6 months duration were screened. A total of 100 participants were randomized 1:1 to multi-catheter cryotherapy or RF. For cryotherapy, a 28-mm Arctic Front Advance was used in tandem with focal cryoablation catheters. Open-irrigated, non-force sensing catheters were used in the RF group with a 3D mapping system. Pulmonary vein (PV) isolation and non-PV triggers were targeted. Participants were followed up at 6 and 12 months, then yearly. Acute PVI was achieved in all cases. More patients in the multi-catheter cryotherapy group were restored to SR by ablation alone, with a shorter procedure duration. Sinus rhythm continued to the last available follow-up in 16/49 patients (33%) in the multi-catheter at 3.0 ± 1.6 years post-ablation and in 12/50 patients (24%) in the RF group at 4.0 ± 1.2 years post-ablation. The yearly rate of arrhythmia recurrence was similar. CONCLUSION: Multi-catheter cryotherapy can restore SR by ablation alone in more cases and more quickly than RF ablation. Long-term success is difficult to achieve by either methods and is similar with both.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Ablação por Radiofrequência , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Catéteres , Crioterapia , Humanos , Veias Pulmonares/cirurgia , Resultado do TratamentoRESUMO
AIMS: Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS: A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION: Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.
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Fibrilação Atrial , Ablação por Cateter , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Esôfago/cirurgia , Humanos , Estudos Prospectivos , Temperatura , Resultado do TratamentoRESUMO
BACKGROUND: Small series has shown that cardiac resynchronisation therapy (CRT) can be achieved in a majority of patients using exclusively cephalic venous access. We sought to determine whether this method is suitable for widespread use. METHODS: A group of 19 operators including 11 trainees in three pacing centres attempted to use cephalic access alone for all CRT device implants over a period of 8 years. The access route for each lead, the procedure outcome, duration, and complications were collected prospectively. Data were also collected for 105 consecutive CRT device implants performed by experienced operators not using the exclusively cephalic method. RESULTS: A new implantation of a CRT device using exclusively cephalic venous access was attempted in 1091 patients (73.6% male, aged 73 ± 12 years). Implantation was achieved using cephalic venous access alone in 801 cases (73.4%) and using a combination of cephalic and other access in a further 180 (16.5%). Cephalic access was used for 2468 of 3132 leads implanted (78.8%). Compared to a non-cephalic reference group, complications occurred less frequently (69/1091 vs 12/105; P = .0468), and there were no pneumothoraces with cephalic implants. Procedure and fluoroscopy duration were shorter (procedure duration 118 ± 45 vs 144 ± 39 minutes, P < .0001; fluoroscopy duration 15.7 ± 12.9 vs 22.8 ± 12.2 minutes, P < .0001). CONCLUSIONS: CRT devices can be implanted using cephalic access alone in a substantial majority of cases. This approach is safe and efficient.
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Veia Axilar , Dispositivos de Terapia de Ressincronização Cardíaca , Cateterismo Periférico/métodos , Competência Clínica , Idoso , Terapia de Ressincronização Cardíaca/métodos , Feminino , Humanos , Masculino , Estudos ProspectivosAssuntos
Bronquiectasia/etiologia , COVID-19/complicações , Trombose Coronária/etiologia , Pneumotórax/etiologia , Embolia Pulmonar/etiologia , Bronquiectasia/diagnóstico por imagem , Trombose Coronária/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Pneumotórax/diagnóstico por imagem , Embolia Pulmonar/diagnóstico por imagemRESUMO
BACKGROUND: Patients with existing or anticipated indications for cardiac resynchronisation therapy (CRT), bradycardia, or anti-tachycardia pacing should not be offered subcutaneous defibrillators (SQIDs) but it remains unclear how clinicians should predict future need for these therapies. METHODS: We applied three SQID selection policies to data collected retrospectively from transvenous implantable cardioverter defibrillator (TV-ICD) implants: (a) approach A, SQID used in inherited channelopathies and idiopathic ventricular fibrillation only; (b) approach B, as above, plus all hypertrophic cardiomyopathy and grown-up congenital heart disease patients; (c) approach C, as above, plus primary and secondary prevention (for ventricular fibrillation only) of SCD in patients with QRS <150 ms. Approach C reflects current ESC and AHA/ACC/HRS guidelines. RESULTS: 338 of 951 patients with TV-ICD were considered for SQID after excluding 613 patients with contraindications. Approaches A, B, and C yielded 45 (4.7%), 89 (9.4%), and 338 (35.5%) patients suitable for SQID, respectively. Use of SQID resulted in more frequent ICD shocks compared to TV-ICD with approach C only (0.43 vs 0.23 per 1000 patient-days; P = .03). Rates of CRT upgrade were comparable across selection criteria (0, 0.03, and 0.07 per 1000 patient-days for approaches A, B, and C, respectively; P = NS). Risk of early mortality was higher when more liberal inclusion criteria were used (P = .003). CONCLUSIONS: One in three patients receiving ICDs may be suitable for SQID under current ESC and AHA/ACC/HRS guidelines. This proportion is influenced significantly by the selection criteria used, and the criteria used by a physician should be informed by the estimated survival of the patient, risk of shocks for MVT, future pacing, and CRT requirements.
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Dispositivos de Terapia de Ressincronização Cardíaca , Terapia de Ressincronização Cardíaca , Seleção de Pacientes , Implantação de Prótese/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosAssuntos
Fibrilação Atrial/diagnóstico , Técnicas Eletrofisiológicas Cardíacas , Sistema de Condução Cardíaco/fisiopatologia , Síndromes de Pré-Excitação/diagnóstico , Taquicardia/diagnóstico , Potenciais de Ação , Idoso , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/cirurgia , Estimulação Cardíaca Artificial , Ablação por Cateter , Diagnóstico Diferencial , Eletrocardiografia , Feminino , Sistema de Condução Cardíaco/cirurgia , Frequência Cardíaca , Humanos , Síndromes de Pré-Excitação/fisiopatologia , Síndromes de Pré-Excitação/cirurgia , Valor Preditivo dos Testes , Taquicardia/fisiopatologia , Taquicardia/cirurgia , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: We sought to analyze the percutaneous coronary intervention (PCI) outcomes of very elderly patients (V. Eld. group, age >80 years) and compare their outcomes to a less elderly cohort (Eld. group, age 75-80 years) traditionally reported in the literature. BACKGROUND: Limited data exist on peri-procedural and long-term outcomes following PCI in the V. Eld. (age >80 years), with under-representation of this cohort in randomized controlled trials. These patients present with advanced complex coronary disease and multiple comorbidities. METHODS: All 580 consecutive patients aged ≥75 years (age 80 ± 4.9 years, 57.4% males) undergoing PCI between April 2006 and November 2011 were included. A total of 624 consecutive lesions were identified and analyzed. All V. Eld. patients (n = 253) were subsequently selected, and their outcomes compared to Eld. patients (n = 327). Mean follow-up was 30.8 ± 2.7 months with 98% clinical follow-up achieved. RESULTS: All comparative data are expressed as (V. Eld. vs Eld.) unless otherwise specified. All-cause mortality was significantly higher in the V. Eld. group (11.9% vs 6.1%), although this did not translate into a significant difference in cardiac mortality (6.3% vs 3.7%) or major adverse cardiac and cerebrovascular events (16.2% vs 12.5%). The composite incidence of myocardial infarction (MI), stroke, definite/probable stent thrombosis, and TIMI major bleed was 4.7%, 1.4% 1.9%, and 6.4%, respectively with no significant difference between both cohorts. CONCLUSIONS: This study demonstrates an acceptable occurrence of MI, death, repeat intervention, and stent thrombosis in a high-risk group of V. Eld. patients with de novo lesions. Age alone in the absence of other non-cardiac factors should not prohibit a patient from access to PCI.
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Doença da Artéria Coronariana/cirurgia , Intervenção Coronária Percutânea/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Doença da Artéria Coronariana/mortalidade , Feminino , Oclusão de Enxerto Vascular/epidemiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Infarto do Miocárdio/epidemiologia , Seleção de Pacientes , Acidente Vascular Cerebral/epidemiologia , Fatores de Tempo , Resultado do TratamentoAssuntos
Apêndice Atrial/fisiologia , Fibrilação Atrial/cirurgia , Ablação por Cateter , Anticoagulantes/uso terapêutico , Apêndice Atrial/diagnóstico por imagem , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Bloqueio Atrioventricular/diagnóstico por imagem , Bloqueio Atrioventricular/etiologia , Bloqueio Atrioventricular/fisiopatologia , Ecocardiografia Doppler de Pulso , Ecocardiografia Transesofagiana , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , ReoperaçãoRESUMO
AIMS: Old age and diabetes are risk factors that often coexist increasing the vulnerability of the heart to the lethal effects of ischaemia-reperfusion injury (IRI). However, to our knowledge, no investigations have examined IRI and cardioprotective signalling in animal models bearing these co-morbidities concomitantly. The ability of the heart to recover following IRI is greatly dependent on its innate cardioprotective potential, in which a central role is played by Akt. We aimed to investigate in an aging diabetic rat model, the susceptibility of the heart to IRI, the achievability of ischaemic preconditioning (IPC) against this lethal event, and the changes in Akt signalling, as the main prosurvival intracellular pathway. METHODS AND RESULTS: Our data showed that the isolated hearts of aged, diabetic Goto-Kakizaki rats were more susceptible to sub-lethal injury and not amenable to cardioprotection via IPC, compared with younger diabetic rat hearts. Western blot analysis of the heart tissue suggested a chronic up-regulation of Akt phosphorylation, and reduced expression of the mitochondrial regulator PGC-1α and of the anti-oxidant enzyme catalase, potentially due to the Akt up-regulation. Moreover, no further activation of Akt could be achieved following IPC. CONCLUSION: An increased susceptibility to IRI in the aged, diabetic heart could be a consequence of impaired Akt signalling due to chronic Akt phosphorylation. Additional Akt phosphorylation required for IPC protection may therefore not be possible in the aged, diabetic rat heart and may explain why this cardioprotective manoeuvre cannot be achieved in these hearts.
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Envelhecimento/fisiologia , Diabetes Mellitus/fisiopatologia , Precondicionamento Isquêmico Miocárdico , Traumatismo por Reperfusão Miocárdica/etiologia , Proteínas Proto-Oncogênicas c-akt/fisiologia , Transdução de Sinais/fisiologia , Animais , Glicemia/análise , Hemoglobinas Glicadas/análise , Humanos , Masculino , Infarto do Miocárdio/etiologia , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Fenótipo , Fosforilação , Ratos , Ratos Wistar , Fatores de Transcrição/fisiologiaRESUMO
Cardiovascular risk led to the withdrawal of Vioxx (rofecoxib) in 2004. Some related drugs also increase cardiovascular risk and cyclooxygenase (COX)-2 inhibitors that remain on the market, including unselective non-steroidal anti-inflammatory drugs (NSAIDs), have not been exonerated. This article reviews if new evidence should change clinical and regulatory practice. Substantial COX-2 inhibition increases the incidence of cardiovascular disease unless concomitant platelet thromboxane production is inhibited by >95%. This can be investigated using whole blood assays, an approach used recently to show that acetaminophen (paracetamol) is a COX-2-selective inhibitor. The epidemiology available suggests acetaminophen, though readily available over-the-counter, does increase cardiovascular risk. Current evidence is inadequate to recommend many potential alternatives to Vioxx as safe. We argue that the precautionary principle, 'first do no harm', should underpin the regulation and prescribing of NSAIDs. Labelling which identifies these risks for prescribers and consumers should be mandatory.
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Doenças Cardiovasculares/induzido quimicamente , Inibidores de Ciclo-Oxigenase/efeitos adversos , Rotulagem de Medicamentos/legislação & jurisprudência , Animais , Humanos , RiscoRESUMO
BACKGROUND: Cardiac amyloidosis can be diagnostically challenging. Cardiovascular magnetic resonance (CMR) can assess abnormal myocardial interstitium. METHODS AND RESULTS: Late gadolinium enhancement CMR was performed in 30 patients with cardiac amyloidosis. In 22 of these, myocardial gadolinium kinetics with T1 mapping was compared with that in 16 hypertensive controls. One patient had CMR and autopsy only. Subendocardial T1 in amyloid patients was shorter than in controls (at 4 minutes: 427+/-73 versus 579+/-75 ms; P<0.01), was shorter than subepicardium T1 for the first 8 minutes (P< or =0.01), and was correlated with markers of increased myocardial amyloid load, as follows: left ventricular (LV) mass (r=-0.51, P=0.013); wall thickness (r=-0.54 to -0.63, P<0.04); interatrial septal thickness (r=-0.52, P=0.001); and diastolic function (r=-0.42, P=0.025). Global subendocardial late gadolinium enhancement was found in 20 amyloid patients (69%); these patients had greater LV mass (126+/-30 versus 93+/-25 g/m2; P=0.009) than unenhanced patients. Histological quantification showed substantial interstitial expansion with amyloid (30.5%) but only minor fibrosis (1.3%). Amyloid was dominantly subendocardial (42%) compared with midwall (29%) and subepicardium (18%). There was 97% concordance in diagnosis of cardiac amyloid by combining the presence of late gadolinium enhancement and an optimized T1 threshold (191 ms at 4 minutes) between myocardium and blood. CONCLUSIONS: In cardiac amyloidosis, CMR shows a characteristic pattern of global subendocardial late enhancement coupled with abnormal myocardial and blood-pool gadolinium kinetics. The findings agree with the transmural histological distribution of amyloid protein and the cardiac amyloid load and may prove to have value in diagnosis and treatment follow-up.