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1.
J Heart Lung Transplant ; 42(8): 1131-1139, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37037751

RESUMO

BACKGROUND: Aim of this study was to describe the real-world use of extracorporeal photopheresis (ECP) and assess its impact on clinical outcomes in the modern era of heart transplantation. METHODS: Seven transplant centers from 5 European countries participated in this retrospective, observational, single-arm chart review study. All patients received ECP after heart transplantation in 2015 or later. Data were extracted from medical records between November 2020 and December 2021. RESULTS: Overall, 105 patients were enrolled and followed for an average of 2 years after initiation of ECP. Reasons to start ECP were acute cellular rejection (35.2%), rejection prevention (32.4%), mixed rejection (18.1%), and antibody-mediated rejection (14.3%). Rejection ISHLT grades improved from start to end of ECP treatment in 92% of patients treated with ECP for rejection. Of patients who started ECP to prevent rejection, 88% remained free from any rejection despite a reduction of calcineurin inhibitors. Overall survival was 95%, and no deaths were related to ECP. Safety events occurred in 18 patients, of which 13 experienced complications with venous access. CONCLUSIONS: This study, the largest European ECP study in heart transplantation, demonstrates that ECP can effectively be used to treat different rejection types and to prevent rejection in the modern era of immunosuppression. Patients with rejections who have received ECP have shown high response as measured by histological improvements in ISHLT classification. A high percentage of patients in the prevention group remained free from rejection despite reduction in immunosuppression, in particular calcineurin inhibitors.


Assuntos
Transplante de Coração , Fotoferese , Humanos , Estudos Retrospectivos , Inibidores de Calcineurina , Terapia de Imunossupressão , Rejeição de Enxerto/prevenção & controle
2.
J Cardiovasc Surg (Torino) ; 63(6): 734-741, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35913035

RESUMO

BACKGROUND: In thoracic aortic surgery, fluid replacement and blood transfusion during extracorporeal circulation (ECC) are associated with increased coagulopathy, elevated inflammatory response, and end-organ dysfunction. The optimal strategy has not been established in this regard. The aim of this study was to evaluate the effect of the fluid balance during ECC in thoracic aortic dissection surgery on outcome. METHODS: Between 2009 and 2020, 358 patients suffering from acute type A aortic dissection (ATAAD) underwent aortic surgery at our heart center. In-hospital mortality, major complications (postoperative stroke, respiratory failure, heart failure, acute renal failure), and follow-up mortality were assessed. Logistic regression analysis was used to identify whether fluid balance and blood transfusion during ECC were risk factors for occurring adverse events. RESULTS: The in-hospital mortality amounted to 20.4%. Major complications included temporary neurologic deficit in 13.4%, permanent neurologic deficit in 6.1%, acute renal failure in 32.7%, prolonged ventilation for respiratory failure in 17.9%, and acute heart failure in 10.9% of cases. At a mean of 42 months after discharge of 285 survivors, follow-up mortality was 13.3%. Multivariate analysis revealed major complications as well as the risk of in-hospital and follow-up mortality to increase with fluid balance and blood transfusion during ECC. CONCLUSIONS: Fluid balance and blood transfusion during ECC present with predictive potential concerning the risk of postoperative adverse events.


Assuntos
Injúria Renal Aguda , Aneurisma da Aorta Torácica , Dissecção Aórtica , Insuficiência Cardíaca , Insuficiência Respiratória , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Dissecção Aórtica/diagnóstico por imagem , Dissecção Aórtica/cirurgia , Dissecção Aórtica/complicações , Circulação Extracorpórea/efeitos adversos , Fatores de Risco , Mortalidade Hospitalar , Transfusão de Sangue , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Equilíbrio Hidroeletrolítico , Insuficiência Cardíaca/complicações , Complicações Pós-Operatórias/etiologia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/complicações
3.
Artif Organs ; 46(9): 1912-1922, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35470442

RESUMO

BACKGROUND: Multiple organ failure is a common complication in patients undergoing ECLS significantly affecting patient outcomes. Gaining knowledge about the mechanisms of onset, clinical course, risk factors, and potential therapeutic targets is highly desirable. METHODS: Data of 354 patients undergoing ECLS with one-, two, three-, and four organ failures were retrospectively analyzed. Incidence of multiple organ dysfunction (MODS), its impact on survival, risk factors for its occurrence, and the impact of proinflammatory mediators on the occurrence of MODS in patients undergoing ECLS were investigated. RESULTS: The median follow-up was 66 (IQR 6; 820) days. 245 (69.2%) patients could be weaned from ECLS, 30-day survival and 1-year survival were 194 (54.1%) and 157 (44.4%), respectively. The duration of mechanical support was 4 (IQR 2; 7) days in the median. Increasing severity of MODS resulted in significant prolongation of mechanical circulatory support and worsening of the outcome. Liver dysfunction had the strongest impact on patient mortality (OR = 2.5) and survival time (19 vs 367 days). The serum concentration of analyzed interleukins rose significantly with each, additional organ affected by dysfunction (p < 0.001). All analyzed proinflammatory cytokines showed significant predictivity relative to the occurrence of MODS with interleukin 8 serum level prior to ECLS showing the strongest predictive potential for the occurrence of MODS (AUC 0.78). CONCLUSION: MODS represents a frequent complication in patients undergoing ECLS with a significant impact on survival. Proinflammatory cytokines show prognostic capacity regarding the occurrence and severity of multi-organ dysfunction.


Assuntos
Oxigenação por Membrana Extracorpórea , Citocinas , Oxigenação por Membrana Extracorpórea/métodos , Humanos , Insuficiência de Múltiplos Órgãos/etiologia , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
4.
Angiology ; 73(3): 252-259, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34362260

RESUMO

The increasing number of patients treated with cardiac implantable electronic devices (CIEDs) and indications for complex pacing requires system revisions. Currently, data on venous patency in repeat CIED surgery involving lead (re)placement or extraction are largely missing. This study aimed to assess venous patency and risk factors in patients referred for repeat CIED lead surgery, emphasizing CIED infection. All consecutive patients requiring extraction, exchange, or additional placement of ≥1 CIED leads during reoperative procedures from January 2015 to March 2020 were evaluated in this retrospective study. Venography was performed in 475 patients. Venous patency could be assessed in 387 patients (81.5%). CIED infection with venous occlusion was detected in 74 patients compared with venous occlusion without infection in 14 patients (P < .05). Concerning venous patency, novel oral anticoagulant medication appeared to be protective (P < .05; odds ratio [OR]: .35). Infection of the CIED appeared to be strongly associated with venous occlusion (OR: 16.0). The sensitivity was only 64.15%, but the specificity was 96.1%. Number of leads involved and previous CIED procedures were not associated with venous occlusion. In conclusion, in patients with CIED, venous occlusion was strongly associated with device infection, but not with the number of leads or previous CIED procedures.


Assuntos
Desfibriladores Implantáveis , Doenças Vasculares , Desfibriladores Implantáveis/efeitos adversos , Eletrônica , Humanos , Reoperação/métodos , Estudos Retrospectivos , Doenças Vasculares/etiologia
5.
Thorac Cardiovasc Surg ; 70(5): 377-383, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-33368107

RESUMO

BACKGROUND: Over the years, open heart surgery has become more complex, and especially reoperative surgery, more demanding. The risk of third-time or more sternotomy procedures is unclear. METHODS: We reviewed our institutional experience of 25 years based on two generations of cardiac surgeons in a German university medical center to document frequency, outcome, and complications of the various types of open heart procedures. RESULTS: Overall, we included 104 patients with a mean age of 64 ± 13 years. The EuroSCORE II (European System for Cardiac Operative Risk Evaluation) calculated an average mortality risk of 15.7 ± 15.4%. Subgroup comparison of isolated coronary artery bypass grafting (CABG), aortic valve replacement, and mitral valve replacement procedures did not delineate significantly different risk profiles except for the incidence of acute myocardial infarction, which was present in every second patient (53.3%) scheduled for CABG surgery. The time interval to previous surgery was 4.7 ± 6.3 years on average. Most frequent surgical procedures were valve operations, which were accomplished in 72 patients (69.2%), whereas coronary bypass surgery was performed in 23 patients (22.1%) only. Combined procedures were performed in 27 patients. Complex aortic arch replacement with a frozen elephant trunk procedure was necessary in six patients. Overall, 30-day survival was 81.7%. CONCLUSION: In conclusion, third-time and more sternotomy procedures offer acceptable outcome and should therefore be considered in appropriate patients.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Implante de Prótese de Valva Cardíaca , Idoso , Humanos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Complicações Pós-Operatórias , Reoperação , Estudos Retrospectivos , Esternotomia/efeitos adversos , Resultado do Tratamento
6.
Heart Rhythm ; 18(12): 2187-2194, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34517118

RESUMO

BACKGROUND: Patients with atrial fibrillation (AF) exhibit decreased atrial expression of connexin (Cx), which has been causally linked to a proarrhythmogenic substrate. Interestingly, patients with sleep-disordered breathing (SDB) are at increased risk of AF, but the mechanisms remain unclear. OBJECTIVE: We tested the hypothesis that patients with SDB have reduced atrial Cx expression independent of important comorbidities. METHODS: We analyzed right atrial appendage biopsies from 77 patients undergoing coronary artery bypass grafting. Patients were tested for SDB by polygraphy before surgery. Expression of Cx40 and Cx43 messenger RNA was quantified using real-time quantitative polymerase chain reaction and Western blot (Cx43). Structural atrial remodeling was investigated histologically and by quantitative polymerase chain reaction. Postoperative AF was assessed by 12-lead electrocardiography. RESULTS: Patients were stratified according to apnea-hypopnea index (SDB if apnea-hypopnea index ≥15 per hour, n = 32 vs n = 45). Patients with SDB had significantly lower atrial Cx43 expression, which was negatively correlated with apnea-hypopnea index and oxygen desaturation index. No significant increase in atrial fibrosis or expression of hypertrophy and inflammatory markers was observed. Interestingly, SDB remained the strongest independent predictor of decreased atrial Cx43 expression in a multivariate logistic regression model including age, sex, diabetes, and heart failure with reduced ejection fraction (odds ratio 7.58; 95% confidence interval 1.891-30.375; P = .004). Moreover, reduced atrial Cx43 expression was strongly associated with the occurrence of postoperative AF (odds ratio 15.749; 95% confidence interval 1.072-231.472; P = .044). CONCLUSION: Patients with SDB exhibited decreased atrial Cx43 expression, which correlated with the severity of SDB. This correlation was independent of several concomitant diseases and may be linked to an increased risk of AF after cardiac surgery.


Assuntos
Fibrilação Atrial , Conexina 43/metabolismo , Perfilação da Expressão Gênica/métodos , Átrios do Coração , Síndromes da Apneia do Sono , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/metabolismo , Fibrilação Atrial/fisiopatologia , Remodelamento Atrial/fisiologia , Ponte de Artéria Coronária/métodos , Eletrocardiografia/métodos , Feminino , Átrios do Coração/metabolismo , Átrios do Coração/patologia , Humanos , Masculino , Polissonografia/métodos , Fatores de Risco , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/metabolismo , Síndromes da Apneia do Sono/fisiopatologia
7.
ESC Heart Fail ; 8(5): 4055-4066, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34196135

RESUMO

AIMS: There is a lack of diagnostic and therapeutic options for patients with atrial cardiomyopathy and paroxysmal atrial fibrillation. Interestingly, an abnormal P-wave terminal force in electrocardiogram lead V1 (PTFV1 ) has been associated with atrial cardiomyopathy, but this association is poorly understood. We investigated PTFV1 as a marker for functional, electrical, and structural atrial remodelling. METHODS AND RESULTS: Fifty-six patients with acute myocardial infarction and 13 kidney donors as control cohort prospectively underwent cardiac magnetic resonance imaging to evaluate the association between PTFV1 and functional remodelling (atrial strain). To further investigate underlying pathomechanisms, right atrial appendage biopsies were collected from 32 patients undergoing elective coronary artery bypass grafting. PTFV1 was assessed as the product of negative P-wave amplitude and duration in lead V1 and defined as abnormal if ≥4000 ms*µV. Activity of cardiac Ca/calmodulin-dependent protein kinase II (CaMKII) was determined by a specific HDAC4 pull-down assay as a surrogate for electrical remodelling. Atrial fibrosis was quantified using Masson's trichrome staining as a measure for structural remodelling. Multivariate regression analyses were performed to account for potential confounders. A total of 16/56 (29%) of patients with acute myocardial infarction, 3/13 (23%) of kidney donors, and 15/32 (47%) of patients undergoing coronary artery bypass grafting showed an abnormal PTFV1 . In patients with acute myocardial infarction, left atrial (LA) strain was significantly reduced in the subgroup with an abnormal PTFV1 (LA reservoir strain: 32.28 ± 12.86% vs. 22.75 ± 13.94%, P = 0.018; LA conduit strain: 18.87 ± 10.34% vs. 10.17 ± 8.26%, P = 0.004). Abnormal PTFV1 showed a negative correlation with LA conduit strain independent from clinical covariates (coefficient B: -7.336, 95% confidence interval -13.577 to -1.095, P = 0.022). CaMKII activity was significantly increased from (normalized to CaMKII expression) 0.87 ± 0.17 to 1.46 ± 0.15 in patients with an abnormal PTFV1 (P = 0.047). This increase in patients with an abnormal PTFV1 was independent from clinical covariates (coefficient B: 0.542, 95% confidence interval 0.057 to 1.027, P = 0.031). Atrial fibrosis was significantly lower with 12.32 ± 1.63% in patients with an abnormal PTFV1 (vs. 20.50 ± 2.09%, P = 0.006), suggesting PTFV1 to be a marker for electrical but not structural remodelling. CONCLUSIONS: Abnormal PTFV1 is an independent predictor for impaired atrial function and for electrical but not for structural remodelling. PTFV1 may be a promising tool to evaluate patients for atrial cardiomyopathy and for risk of atrial fibrillation.


Assuntos
Fibrilação Atrial , Remodelamento Atrial , Fibrilação Atrial/diagnóstico , Eletrocardiografia , Átrios do Coração/diagnóstico por imagem , Humanos , Fatores de Risco
9.
Mol Cell Biochem ; 472(1-2): 79-94, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32564294

RESUMO

Heart transplantation is often an unrealizable therapeutic option for end-stage heart failure, which is why mechanical left ventricular assist devices (LVADs) become an increasingly important therapeutic alternative. Currently, there is a lack of information about molecular mechanisms which are influenced by LVADs, particularly regarding the pathophysiologically critical renin angiotensin system (RAS). We, therefore, determined regulation patterns of key components of the RAS and the ß-arrestin signaling pathways in left ventricular (LV) tissue specimens from 8 patients with end-stage ischemic cardiomyopathy (ICM) and 12 patients with terminal dilated cardiomyopathy (DCM) before and after LVAD implantation and compared them with non-failing (NF) left ventricular tissue samples: AT1R, AT2R, ACE, ACE2, MasR, and ADAM17 were analyzed by polymerase chain reaction. ERK, phosphorylated ERK, p38, phosphorylated p38, JNK, phosphorylated JNK, GRK2, ß-arrestin 2, PI3K, Akt, and phosphorylated Akt were determined by Western blot analysis. Angiotensin I and Angiotensin II were quantified by mass spectrometry. Patients were predominantly middle-aged (53 ± 10 years) men with severely impaired LV function (LVEF 19 ± 8%), when receiving LVAD therapy for a mean duration of 331 ± 317 days. Baseline characteristics did not differ significantly between ICM and DCM patients. By comparing failing with non-failing left ventricles, i.e., before LVAD implantation, a downregulation of AT1R, AT2R, and MasR and an upregulation of ACE, ACE2, GRK, ß-arrestin, ERK, PI3K, and Akt were seen. Following LVAD support, then angiotensin I, ACE2, GRK, and ß-arrestin were downregulated and AT2R, JNK, and p38 were upregulated. ACE, angiotensin II, AT1R, ADAM17, MasR, ERK, PI3K, and Akt remained unchanged. Some regulation patterns were influenced by the underlying etiology of heart failure, the severity of LV dysfunction at baseline, and the duration of LVAD therapy. Key components of the RAS and ß-arrestin signaling pathways were divergently altered in failing left ventricles both before and after LVAD implantation, whereas a remarkable fraction remained unchanged. This indicates a rather incomplete molecular reverse remodeling, whose functional relevance has to be further evaluated.


Assuntos
Angiotensina II/metabolismo , Angiotensina I/metabolismo , Insuficiência Cardíaca/metabolismo , Coração Auxiliar , Sistema Renina-Angiotensina , beta-Arrestinas/metabolismo , Proteínas ras/metabolismo , Feminino , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Proto-Oncogene Mas , Transdução de Sinais
10.
Artif Organs ; 44(8): 837-845, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32043591

RESUMO

Extracorporeal life support is increasingly used in the treatment of patients presenting with cardiogenic shock or in need of cardiopulmonary resuscitation. Identifying therapeutic targets and factors associated with the prognosis are highly desirable. The present study analyzed the impact of interleukin 6 and 8 on the outcome of patients undergoing venoarterial extracorporeal membrane oxygenation (VA ECMO). Interleukin 6 and 8 serum levels of 329 patients were analyzed prior to, on days 1 and 5 of VA ECMO therapy. Interleukin 6 and 8 serum levels of surviving and nonsurviving patients were compared. At time points with significant differences, receiver operating characteristics and cutoff levels were analyzed to determine the prognostic value of interleukin serum levels. Survival analysis was performed to compare patients above and below cutoff levels. Interleukin 6 serum levels were significantly elevated in nonsurviving patients prior to VA ECMO initiation. Interleukin 6 and 8 serum levels in nonsurviving patients were significantly elevated on day 1 of VA ECMO. Receiver operating characteristics analysis revealed significant prognostic impact of interleukin 6 and 8 on day 1 of VA ECMO (AUC 0.70 and 0.72). Survival analysis comparing patients above and below the cutoff showed a 1-year survival of 32.6% for IL6 and 20.8% for IL8 above, as well as 66.9% for IL6 and 61.9% for IL8 below the cutoff (P < .05). Interleukin 6 and 8 serum levels demonstrated prognostic value early in VA ECMO therapy. The technical applicability of interleukin reduction raises interest in interleukins 6 and 8 as therapeutic targets.


Assuntos
Oxigenação por Membrana Extracorpórea/mortalidade , Interleucinas/sangue , Biomarcadores/sangue , Oxigenação por Membrana Extracorpórea/efeitos adversos , Feminino , Humanos , Interleucina-6/sangue , Interleucina-8/sangue , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Curva ROC , Análise de Sobrevida
11.
Artif Organs ; 43(6): 542-550, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30411818

RESUMO

The use of minimized cardiopulmonary bypass support to reduce the side effects of extracorporeal circulation is still contradictorily discussed. This study compares perfusion operated by conventional (CCPB) and minimized (MCPB) cardiopulmonary bypass support during coronary artery bypass grafting (CABG). This study includes the data of 5164 patients treated at our department between 2004 and 2014. Tissue perfusion during cardiopulmonary bypass support and cardiac arrest was assessed by means of body mass index, hemodilution, blood pressure with corresponding pump flow and venous oxygen saturation, serum lactate, and serum pH. Hemodilution was more pronounced after CCPB: hemoglobin had dropped to 4.47 ± 0.142 g/dL after CCPB and to 2.77 ± 0.148 g/dL after MCPB (P = 0.0022). Despite the higher pump flow in conventional circuits (4.86-4.95 L/min vs. 4.1-4.18 L/min), mean blood pressure was higher during minimized bypass support (53 ± 10 vs. 56 ± 13 mm Hg [aortic clamping], 57 ± 9 vs. 61 ± 12 mm Hg [34°C], 55 ± 9 vs.59 ± 11 mm Hg [aortic clamp removal], P < 0.0001) at all time points. Venous oxygen saturation remained on comparable levels of >70% during both conventional and minimized cardiopulmonary bypass support. The increase in serum lactate was more pronounced after CCPB (8.98 ± 1.28 vs. 3.66 ± 1.25 mg/dL, P = 0.0079), corresponding to a decrease in serum pH to acidotic levels (7.33 ± 0.06 vs. 7.35 ± 0.06, P < 0.0001). These effects were evident in all BMI ranges. Minimized cardiopulmonary bypass support provides efficient perfusion in all BMI ranges and is thus equivalent to conventional circuits.


Assuntos
Ponte Cardiopulmonar/métodos , Ponte de Artéria Coronária/métodos , Idoso , Pressão Arterial , Índice de Massa Corporal , Estudos de Coortes , Feminino , Hemoglobinas/análise , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade
12.
J Cardiothorac Surg ; 13(1): 102, 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285786

RESUMO

BACKGROUND: In cases of lead failure after implantation of pacemakers (PM) or implantable cardioverter defibrillators (ICD) early lead replacement may be challenging. Puncture of the subclavian vein bears possible complications such as pneumothorax, hematothorax, and damage of leads to be left in place. To avoid venous puncture PM or ICD leads were replaced using a flexible polypropylene sheath (Byrd-sheath). METHOD: From January 2010 through December 2017, 55 patients underwent early lead exchange avoiding venous puncture. Early lead exchange for this study was defined as a reintervention within 14 days after the initial lead implantation. The connector of the malfunctioning lead was cut off, and stabilized by a stiff stylet. After having cut off the plastic knob of the stylet, the lead was passed through the polypropylene sheath and the latter advanced into the subclavian vein with gentle rotational movements to gain access to the subclavian vein. After lead removal the polypropylene sheath was replaced by a peel away sheath a new lead inserted. RESULTS: Overall, 23 defibrillation leads and 34 pacing leads (16 right atrial leads, 17 right ventricular leads, and 1 left ventricular lead) were successfully explanted. Access to the subclavian vein was uneventful, and blood loss minimal. Radiation exposure and fluoroscopy time were also negligible. CONCLUSION: The Byrd-sheath technique proved to be safe and successful in providing vein access within 2 weeks after initial lead implantation using the previously implanted lead and thus avoiding puncture of the subclavian vein.


Assuntos
Estimulação Cardíaca Artificial/efeitos adversos , Desfibriladores Implantáveis/efeitos adversos , Remoção de Dispositivo/métodos , Marca-Passo Artificial/efeitos adversos , Lesões do Sistema Vascular/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Estimulação Cardíaca Artificial/métodos , Remoção de Dispositivo/efeitos adversos , Desenho de Equipamento/efeitos adversos , Desenho de Equipamento/métodos , Falha de Equipamento , Feminino , Fluoroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Polipropilenos , Punções , Estudos Retrospectivos , Veia Subclávia/lesões , Veia Subclávia/cirurgia , Fatores de Tempo , Lesões do Sistema Vascular/etiologia
13.
ESC Heart Fail ; 5(4): 642-648, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30117720

RESUMO

AIMS: The EMPA-REG OUTCOME study showed reduced mortality and hospitalization due to heart failure (HF) in diabetic patients treated with empagliflozin. Overexpression and Ca2+ -dependent activation of Ca2+ /calmodulin-dependent kinase II (CaMKII) are hallmarks of HF, leading to contractile dysfunction and arrhythmias. We tested whether empagliflozin reduces CaMKII- activity and improves Ca2+ -handling in human and murine ventricular myocytes. METHODS AND RESULTS: Myocytes from wild-type mice, mice with transverse aortic constriction (TAC) as a model of HF, and human failing ventricular myocytes were exposed to empagliflozin (1 µmol/L) or vehicle. CaMKII activity was assessed by CaMKII-histone deacetylase pulldown assay. Ca2+ spark frequency (CaSpF) as a measure of sarcoplasmic reticulum (SR) Ca2+ leak was investigated by confocal microscopy. [Na+ ]i was measured using Na+ /Ca2+ -exchanger (NCX) currents (whole-cell patch clamp). Compared with vehicle, 24 h empagliflozin exposure of murine myocytes reduced CaMKII activity (1.6 ± 0.7 vs. 4.2 ± 0.9, P < 0.05, n = 10 mice), and also CaMKII-dependent ryanodine receptor phosphorylation (0.8 ± 0.1 vs. 1.0 ± 0.1, P < 0.05, n = 11 mice), with similar results upon TAC. In murine myocytes, empagliflozin reduced CaSpF (TAC: 1.7 ± 0.3 vs. 2.5 ± 0.4 1/100 µm-1  s-1 , P < 0.05, n = 4 mice) but increased SR Ca2+ load and Ca2+ transient amplitude. Importantly, empagliflozin also significantly reduced CaSpF in human failing ventricular myocytes (1 ± 0.2 vs. 3.3 ± 0.9, P < 0.05, n = 4 patients), while Ca2+ transient amplitude was increased (F/F0 : 0.53 ± 0.05 vs. 0.36 ± 0.02, P < 0.05, n = 3 patients). In contrast, 30 min exposure with empagliflozin did not affect CaMKII activity nor Ca2+ -handling but significantly reduced [Na+ ]i . CONCLUSIONS: We show for the first time that empagliflozin reduces CaMKII activity and CaMKII-dependent SR Ca2+ leak. Reduced Ca2+ leak and improved Ca2+ transients may contribute to the beneficial effects of empagliflozin in HF.


Assuntos
Compostos Benzidrílicos/farmacologia , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Cálcio/metabolismo , Glucosídeos/farmacologia , Ventrículos do Coração/metabolismo , Miócitos Cardíacos/metabolismo , Animais , Western Blotting , Sinalização do Cálcio , Células Cultivadas , Modelos Animais de Doenças , Ventrículos do Coração/efeitos dos fármacos , Ventrículos do Coração/patologia , Camundongos , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
14.
Resuscitation ; 93: 53-7, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26051810

RESUMO

BACKGROUND: Interhospital transfer of patients experiencing circulatory failure and shock has a significant risk of cardiovascular deterioration and death. Extracorporeal life support (ECLS) is a rescue tool for hemodynamic stabilization that makes patient transportation much safer. METHODS: Demographic data, clinical course, and outcome data were reviewed for patients who underwent placement of a venoarterial ECLS in a remote hospital and were transported to our tertiary care facility. RESULTS: 68 patients were transported to our center with ECLS. The majority of these patients (79%) underwent cardiopulmonary resuscitation during or immediately prior to ECLS initiation. The mean patient age was 52 years, and 53 patients were male. The most common underlying diagnosis was acute coronary syndrome (60%). Overall, 23 patients underwent consecutive cardiosurgical procedures, including coronary artery bypass grafting in 12, and left ventricular assist device and biventricular assist device implantation in 11. The median duration of ECLS was 5 days. None of the patients died during transportation. Twelve of the surgically treated patients survived, as well as 21 patients with non-surgical treatment, which resulted in an overall survival of 33 patients (48.5%). CONCLUSION: ECLS-facilitated patient transfer enables safe interhospital transfer of critically ill patients. In this study, a relevant percentage of patients were in need of a cardiosurgical intervention. The long-term survival rate of these patients supports the further use of this time-, cost- and personnel-demanding strategy.


Assuntos
Síndrome Coronariana Aguda/complicações , Reanimação Cardiopulmonar , Oxigenação por Membrana Extracorpórea , Parada Cardíaca , Efeitos Adversos de Longa Duração , Choque , Síndrome Coronariana Aguda/fisiopatologia , Terapia de Ressincronização Cardíaca/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/mortalidade , Oxigenação por Membrana Extracorpórea/métodos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Alemanha/epidemiologia , Parada Cardíaca/etiologia , Parada Cardíaca/terapia , Hemodinâmica , Humanos , Efeitos Adversos de Longa Duração/epidemiologia , Efeitos Adversos de Longa Duração/etiologia , Efeitos Adversos de Longa Duração/prevenção & controle , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Gestão de Riscos/métodos , Choque/etiologia , Choque/terapia , Transporte de Pacientes/métodos
15.
J Cardiothorac Surg ; 9: 20, 2014 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-24438155

RESUMO

BACKGROUND: Postoperative Acute Kidney Injury (AKI) after coronary artery bypass grafting (CABG) is a common complication associated with significant morbidity and mortality. Cardiopulmonary bypass (CPB) is accepted to contribute to the occurrence of AKI and is of particular importance as it can be avoided by using the off-pump technique. However the renoprotective properties of off-pump (CABG) are controversial. This analysis evaluates the impact of cardiopulmonary bypass on renal function. METHODS: A matched-pair analysis of 1428 patients undergoing coronary artery bypass grafting was conducted. The patients were stratified according to their preoperative renal function and to risk factors for postoperative AKI. The development of the glomerular filtration rate (GFR) from before surgery until hospital discharge was analyzed. Incidence of AKI were analyzed. Furthermore the impact of CPB duration on postoperative GFR was assessed. RESULTS: The occurrence of AKI increases the risk of thirty-day mortality (odds ratio of 4.3). The postoperative GFR decreases significantly after coronary artery bypass grafting but does not differ between onpump and offpump CABG (60.2 ± 24.5 vs 60.7 ± 24.8; p=0.54). No difference regarding the incidence (26.6% vs 25%) and severity of AKI between cardiopulmonary bypass and the off-pump technique could be found. Duration of cardiopulmonary bypass does not correlate with the decline in postoperative glomerular filtration rate (Pearson Product Moment Correlation; p>0.050). CONCLUSION: Neither the mere use nor duration of cardiopulmonary bypass proofed to be a risk factor for developing postoperative AKI in CABG patients with a comparable preoperative risk profile for postoperative renal dysfunction. Furthermore, the severity of postoperative AKI is not affected by the use of cardiopulmonary bypass.


Assuntos
Injúria Renal Aguda/epidemiologia , Ponte de Artéria Coronária sem Circulação Extracorpórea/efeitos adversos , Doença da Artéria Coronariana/cirurgia , Complicações Pós-Operatórias/epidemiologia , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Creatinina/sangue , Feminino , Alemanha/epidemiologia , Taxa de Filtração Glomerular , Mortalidade Hospitalar/tendências , Humanos , Incidência , Masculino , Análise por Pareamento , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Fatores de Risco , Taxa de Sobrevida/tendências , Resultado do Tratamento
16.
ASAIO J ; 59(6): 547-53, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24172259

RESUMO

Extracorporeal life support is a worldwide expanding technology for patients in critical cardiogenic shock. The device is usually attached to the femoral vessels using percutaneous techniques. Despite sufficient extracorporeal circulatory support, an unclear number of patients develop high end-diastolic pressures leading to left ventricular distension and pulmonary edema, and ventricular thrombus formation may evolve. This article discusses the strategies to prevent ventricular distension by conservative, interventional, and surgical means, also illustrated by case presentations.


Assuntos
Oxigenação por Membrana Extracorpórea/efeitos adversos , Ventrículos do Coração/cirurgia , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/cirurgia , Descompressão Cirúrgica , Humanos
17.
J Cardiothorac Surg ; 8: 158, 2013 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-23800191

RESUMO

BACKGROUND: Cardiac tamponade is a severe complication after open heart surgery. Diagnostic imaging is challenging in postoperative patients, especially if tamponade develops with subacute symptoms. Hypothesizing that delayed tamponade after open heart surgery is not sufficiently detected by transthoracic echocardiography, in this study CT scans were used as standard reference and were compared with transthoracic echocardiography imaging in patients with suspected cardiac tamponade. METHOD: Twenty-five patients after open heart surgery were enrolled in this analysis. In case of suspected cardiac tamponade patients underwent both echocardiography and CT imaging. Using CT as standard of reference sensitivity, specificity, positive and negative predictive values of ultrasound imaging in detecting pericardial effusion/hematoma were analyzed. Clinical appearance of tamponade, need for re-intervention as well as patient outcome were monitored. RESULTS: In 12 cases (44%) tamponade necessitated surgical re-intervention. Most common symptoms were deterioration of hemodynamic status and dyspnea. Sensitivity, specificity, positive and negative predictive values of echocardiography were 75%, 64%, 75%, and 64% for detecting pericardial effusion, and 33%, 83%, 50, and 71% for pericardial hematoma, respectively. In-hospital mortality of the re-intervention group was 50%. CONCLUSION: Diagnostic accuracy of transthoracic echocardiography is limited in patients after open heart surgery. Suplemental CT imaging provides rapid diagnostic reliability in patients with delayed cardiac tamponade.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Tamponamento Cardíaco/diagnóstico por imagem , Derrame Pericárdico/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Idoso , Idoso de 80 Anos ou mais , Ecocardiografia , Humanos , Pessoa de Meia-Idade , Derrame Pericárdico/diagnóstico por imagem , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento
18.
Artif Organs ; 37(2): 150-6, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23379286

RESUMO

Extracorporeal membrane oxygenation (ECMO) has been successfully used to support patients with cardiac arrest failing to respond to conventional cardiopulmonary resuscitation (CPR). Preimplant factors being indicative for success are unknown up to now. The study describes single center experience with special focus on differences between survivors and nonsurvivors. Between 2002 and 2009, 103 patients were supported within the scope of CPR by means of ECMO. Besides primary diagnosis, duration, and outcome, pH, lactate, mean arterial pressure, aspartate aminotransferase, bilirubin, catecholamine dosage, and oxygenation ratio before ECMO, after 2 h, 1 day, and at explantation were analyzed. One hundred three patients (51.2 ± 16 years, 35 women, 68 men) were analyzed. Primary cardiac failure led to CPR in 54%. Duration of support was 4.8 ± 0.6 days. Twenty-nine (28.1%) patients survived to hospital discharge. On ECMO support, pH, lactate, and mean arterial pressure improved significantly. Catecholamine dosage was significantly reduced after ECMO implantation. Demographic data and primary diagnosis revealed no significant influence on outcome. pH, lactate, creatinine, and bilirubin differed significantly between survivors and nonsurvivors in the course of ECMO support. ECMO support during CPR reliably improves the circulatory and respiratory situation. Considering observed survival critical patient selection is mandatory. Although there are several significant differences between surviving patients and patients with fatal outcome, patient selection turns out to be difficult as clinically relevant factors show only limited predictive value. Future research should focus on better defining a population that may be best of all suited for the use of ECMO support in CPR.


Assuntos
Oxigenação por Membrana Extracorpórea , Parada Cardíaca/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Pressão Arterial , Biomarcadores/sangue , Fármacos Cardiovasculares/uso terapêutico , Catecolaminas/uso terapêutico , Distribuição de Qui-Quadrado , Criança , Pré-Escolar , Estado Terminal , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Alemanha , Parada Cardíaca/sangue , Parada Cardíaca/diagnóstico , Parada Cardíaca/mortalidade , Parada Cardíaca/fisiopatologia , Mortalidade Hospitalar , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
19.
ASAIO J ; 58(6): 616-21, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22990284

RESUMO

Veno-venous extracorporeal membrane oxygenation (vvECMO) conventionally requires the cannulation of two vessels. Here we report our initial experience with the "Wang-Zwische" (WZ) double-lumen cannula. In a group of n = 36 patients single venous cannulation for vvECMO was performed. A retrospective analysis was executed. A comparison of flow characteristics to standard two-vessel cannulation was performed. Mean age of the patient population was 48 ± 15 years (body mass index [BMI] 32 ± 13 kg/m(2)). In n = 32 patients (89%) the cannula was implanted percutaneously under echo or fluoroscopic guidance in less than 30 minutes. Nine patients were partially mobilized on extracorporeal membrane oxygenation (ECMO) support. Oxygenation (partial arterial oxygen tension [PaO(2)]/fraction of inspired oxygen [FiO(2)]) improved significantly in all patients from 66 mm Hg (interquartile range [IQR] 58-87 mm Hg) before ECMO to 117 mm Hg (IQR 95-195 mm Hg, p = 0.001) after 24 hours. In seven patients (19%) nonfatal adverse events occurred, including three dislocations, two partial cannula thrombosis, one ventricular perforation, and one retroperitoneal hemorrhage. The negative pressures for drainage at a flow of 2.5 L/min were significantly lower in a standard (S) two-vessel approach compared with a WZ approach (S: -9 mm Hg; IQR -3 to -24 mm Hg, vs. WZ: -23 mm Hg; IQR -4 to -40 mm Hg; p = 0.04). The WZ cannula offers sufficient gas exchange in addition to certain advantages over standard cannulation, including facilitated cannulation in selected patients and improved mobilization.


Assuntos
Oxigenação por Membrana Extracorpórea , Adulto , Idoso , Cateterismo , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Troca Gasosa Pulmonar
20.
Artif Organs ; 36(8): 700-4, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22882440

RESUMO

A surgical method for the implantation of a mechanical right ventricular assist device which avoids resternotomy/thoracotomy and related complications at the time of explantation is presented. In order to support the failing right heart, a Dacron vascular graft was sewn to the pulmonary artery. For venous drainage, a cannula was inserted into the right atrium via the femoral vein. Explantation of the system, after the right heart resumed its function, was accomplished by retracting and compressing the venous cannula in the groin as well as by retracting the arterial cannula from the Dacron vascular graft followed by suturing without opening the chest. Between 2006 and 2011, this system was used in 12 patients. The median duration of right heart support was 10.5 days. Seven patients were successfully weaned from the system, six patients survived. In all cases, explantation was free of complications. The technique described is a safe method to support the right heart and allows explantation without the risks and complications of reopening the thorax.


Assuntos
Procedimentos Cirúrgicos Cardíacos/métodos , Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Artéria Pulmonar/cirurgia , Adulto , Idoso , Cateterismo , Ecocardiografia , Feminino , Coração/fisiopatologia , Insuficiência Cardíaca/fisiopatologia , Coração Auxiliar/efeitos adversos , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade
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