Chronic systemic glucocorticoid therapy is associated with increased risk of major vascular complications and cardiac tamponade after transcatheter aortic valve implantation: a systematic review and meta-analysis.

INTRODUCTION: TAVI-related complications, such as conduction disturbances, vascular complications or death may be related to increased inflammatory response. The aim of this study was to elucidate the efficacy and safety of the systemic glucocorticoid therapy regarding the adverse events after TAVI deployment. EVIDENCE ACQUISITION: We conducted a systemic search of PubMed, a reference list of relevant articles, and Medline. The main efficacy outcomes of interest were all-cause death, cardiac and non-cardiac death, permanent pacemaker implantation (PPM), new left bundle branch block (LBBB), stroke, and myocardial infarction (MI). Safety endpoints were major vascular complications, major bleeding events, and cardiac tamponade. EVIDENCE SYNTHESIS: A total of 7 studies including data from 3439 patients with a median follow-up was 30 days. Systemic glucocorticoid compared to the control group were associated with an increased risk of non-cardiac death (Relative Risk [RR] 5.90 95%CI [2.95; 11.80], P<0.001) major vascular complications (RR 1.78, 95%CI [1.22 - 2.61], P=0.003) and cardiac tamponade (RR 3.42, 95%CI [1.69 - 6.92], P<0.001). However, there were no differences in all-cause death, cardiac death, new LBBB, stroke, MI, or major bleeding events (all P values >0.05). CONCLUSIONS: Glucocorticoid therapy before the TAVI procedure was associated with an increase in non-cardiac death, major vascular events and cardiac tamponade. There were no differences in the risk of all-cause death, cardiac death, PPM or LBBB, stroke, or MI.

Clinical impact of the infrapatellar location in symptomatic peripheral arterial disease patients / Impacto clínico de la localización infrapatelar en pacientes con enfermedad arterial periférica sintomática

Abstract Background: Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes. Methods: We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints. Results: From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI] = [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients. Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death, MI, stroke, and MACE events were not different among groups (all p > 0.05). Conclusion: Infrapatellar disease was an independent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellar disease in symptomatic revascularized PAD patients.

Resumen Objetivo: La enfermedad vascular periférica (EVP) afecta generalmente múltiples segmentos de los miembros. Existe información contradictoria con respecto al pronóstico de pacientes con enfermedad aortoilíaca, sin embargo, la diabetes y la enfermedad critica de miembros inferiores habitualmente afecta el territorio infrapatelar. Nuestro objetivo es determinar el impacto de la afectación infrapatelar en eventos cardiovasculares. Métodos: Estudio retrospectivo, observacional en un hospital universitario de Argentina. Se revisó la historia clínica electrónica de pacientes con EVP con requerimiento de revascularización. Se generó un modelo de regresión multivariado incluyendo variables clínicamente relevantes. El punto final primario fue un combinado de hospitalización por isquemia crítica y amputaciones mayores entre pacientes con afectación infrapatelar y suprapatelar. Amputaciones menores, muerte por todas las causas, infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV) y un combinado de eventos cardiovasculares (MACE) fueron los puntos secundarios. Resultados: Se reclutó un total de 309 pacientes desde enero de 2014 hasta julio de 2020. 151 pacientes presentaron enfermedad suprapatelar y 158 infrapatelar. El punto final primario ocurrió en 35 pacientes (22.2%) en el grupo infrapatelar y en 18 pacientes (11.9%) en suprapatelares (HR 2.16; intervalo de confianza 95% [1.22-3.82]; p = 0.008). Ambos componentes ocurrieron con mayor frecuencia en pacientes con afectación infrapatelar. Los eventos de amputación menor fueron mas prevalentes en pacientes con afectación infrapatelar (HR 5.09; IC95% [1.47-17.6]; p = 0.010) La mortalidad por todas las causas, IAM, ACV y MACE no fueron diferentes entre los grupos (p > 0.05). Conclusión: La enfermedad infrapatelar fue un factor independiente para mayor riesgo de hospitalización por isquemia critica, amputación mayor y menor comparado con pacientes con afectación suprapatelar en EVP sintomática revascularizada.

Clinical impact of the infrapatellar location in symptomatic peripheral arterial disease patients.

Background: Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes. Methods: We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints. Results: From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI]= [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients.Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death,MI, stroke, and MACE events were not different among groups (all p > 0.05). Conclusion: Infrapatellar disease was anindependent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellardisease in symptomatic revascularized PAD patients.

Objetivo: La enfermedad vascular periférica (EVP) afecta generalmente múltiples segmentos de los miembros. Existe información contradictoria con respecto al pronóstico de pacientes con enfermedad aortoilíaca, sin embargo, la diabetes y la enfermedad critica de miembros inferiores habitualmente afecta el territorio infrapatelar. Nuestro objetivo es determinar el impacto de la afectación infrapatelar en eventos cardiovasculares. Métodos: Estudio retrospectivo, observacional en un hospital universitario de Argentina. Se revisó la historia clínica electrónica de pacientes con EVP con requerimiento de revascularización. Se generó un modelo de regresión multivariado incluyendo variables clínicamente relevantes. El punto final primario fue un combinado de hospitalización por isquemia crítica y amputaciones mayores entre pacientes con afectación infrapatelar y suprapatelar. Amputaciones menores, muerte por todas las causas, infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV) y un combinado de eventos cardiovasculares (MACE) fueron los puntos secundarios. Resultados: Se reclutó un total de 309 pacientes desde enero de 2014 hasta julio de 2020. 151 pacientes presentaron enfermedad suprapatelar y 158 infrapatelar. El punto final primario ocurrió en 35 pacientes (22.2%) en el grupo infrapatelar y en 18 pacientes (11.9%) en suprapatelares (HR 2.16; intervalo de confianza 95% [1.22-3.82]; p = 0.008). Ambos componentes ocurrieron con mayor frecuencia en pacientes con afectación infrapatelar. Los eventos de amputación menor fueron mas prevalentes en pacientes con afectación infrapatelar (HR 5.09; IC95% [1.47-17.6]; p = 0.010) La mortalidad por todas las causas, IAM, ACV y MACE no fueron diferentes entre los grupos (p > 0.05). Conclusión: La enfermedad infrapatelar fue un factor independiente para mayor riesgo de hospitalización por isquemia critica, amputación mayor y menor comparado con pacientes con afectación suprapatelar en EVP sintomática revascularizada.

Chronic treatment with serelaxin mitigates adverse remodeling in a murine model of ischemic heart failure and modulates bioactive sphingolipid signaling.

Relaxin is a pleiotropic hormone demonstrated to confer cardioprotection in animal models of myocardial infarction and ischemic heart failure by modulating inflammation, fibrosis and arrhythmogenesis. Several of these pathways in the ischemic myocardium are intricately tied with the downstream signaling of bioactive sphingolipids, which play an active role during post-infarction remodeling. In this current study, we examined the effects of relaxin on sphingosine 1-phosphate (S1P), and the potential benefits of relaxin treatment on cardiac health in a rodent model of ischemic heart failure. Acute (30 min) and sub-acute (24 h) treatment of primary cardiomyocytes with serelaxin (recombinant human relaxin-2) increased the cardiomyocyte content of S1P. In the rodent model, treatment with relaxin for 28 days following myocardial ischemia by way of permanent left coronary artery occlusion improved survival and cardiac function, reduced fibrosis and apoptosis, and mitigated the expression of several pro-inflammatory and pro-fibrotic markers. The expression of beclin-1 (autophagy marker) was also reduced. The expression of S1P was significantly higher in cardiac tissue and plasma samples extracted from serelaxin-treated mice at day 28. In conclusion, our studies show a significant protection from relaxin in ischemic heart disease, and demonstrate the association between relaxin signaling and S1P generation.

Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio predict in-hospital mortality in symptomatic but unruptured abdominal aortic aneurysm patients.

BACKGROUND: Symptomatic but unruptured abdominal aortic aneurysm (AAA) is a potentially fatal disease since its etiopathogenesis, involving acute changes in the aortic wall, including inflammation, increasing the probability of impending rupture. The objective of the present study was to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and the platelet-to-lymphocyte ratio (PLR) in patients undergoing urgent symptomatic AAA repair. METHODS: This was a retrospective study including 29 patients with symptomatic AAA repaired between 2011 and 2020. Both NLR and PLR were calculated on hospital admission prior to the intervention. The primary end point was in-hospital mortality, and the secondary end point included length of hospital stay and postoperative complications. RESULTS: In-hospital mortality rate was 10.3%. The discriminatory performance to predict the primary end point was very good both for PLR (area under the ROC curve [AUC]: 0.92 (95% confidence interval [CI]: 0.82-1.00; P=0.02) and NLR (AUC: 0.88 [95% CI: 0.75-1.00]; P=0.04). The best cutoff point to predict in-hospital mortality was 185 for PLR (100% sensitivity and 85% specificity) and 6.4 for NLR (100% sensitivity and 77% specificity). The most frequent postoperative complication was acute kidney failure (37.9%). Both elevated PLR as NLR were significantly associated with acute kidney failure and multiorgan failure in the immediate postoperative period (P<0.01). None of the two ratios was associated with length of hospital stay (P=NS). CONCLUSIONS: Both PLR and NLR are low-cost inflammatory markers widely available in every emergency department, with excellent performance to predict in-hospital mortality in patients undergoing symptomatic AAA repair. Patients with a PLR≥185 and/or an NLR≥6.4 could benefit from a "surveyed waiting conduct" improving the preoperative clinical condition prior to the intervention, or even considering endovascular repair.

Novel Common Femoral Artery Lesion Classification in Patients Undergoing Endovascular Revascularization.

PURPOSE: Common femoral artery (CFA) is a critical segment of the lower-limb arterial tree. We sought to propose an extensive classification in order to appraise a diagnostic and therapeutic approach. METHODS: A retrospective cohort of CFA lesions with endovascular therapy was evaluated. We appraised the extension, the degree of stenosis and the calcium burden. A new group "IV" included lesions that started at the external iliac artery or common iliac artery extending into the CFA and affecting its bifurcation. The primary outcome was the need for a retrograde bailout access after failed anterograde access and the procedural time. RESULTS: From 2012 to 2020, a total of 58 lower limbs in patients with CFA lesions were included. New proposed group IV compromised 36% of lesions. Additionally, procedural time was significantly longer in group IV lesions compared with the rest (76.9 ± 32.23 min vs 47.67 ± 17.93 min, p < 0.01), as was the requirement of retrograde bailout access (23.8 vs 2.6%, p = 0.03). Occlusive lesions were associated with longer procedural times and bailout retrograde access compared to stenotic lesions (74.7 ± 33.6 min vs 48.29 ± 16 min, p < 0.001 and 26.1 vs 0%, p = 0.006, respectively), as well as heavy calcification compared to mild or moderate calcification (73.18 ± 28.15 vs 51.86 ± 25.1, p = 0.06 and 29.4 vs 2.4%, p = 0.009, respectively). Secondary clinical outcomes and target lesion revascularization did not differ among groups. CONCLUSIONS: Our classification includes a new group of extensive and frequent lesions, which did not fit in previous classifications.

Additive prognosis of clinical presentation in revascularized peripheral arterial disease patients.

BACKGROUND: Peripheral artery disease (PAD) is a frequent cause of morbidity and mortality. It may present with diverse clinical presentations. The aim of this study was to evaluate the prognosis of these clinical presentations. METHODS: We performed a retrospective cohort study, in which symptomatic PAD patients were included from 2014 to 2020 at a university hospital in Argentina. We classified symptomatic PAD in intermittent claudication (IC), chronic limb-threatening ischemia (CLTI) and acute ischemia (AI). Our primary endpoint was to compare the composite of all-cause mortality and major amputation events between the three groups. RESULTS: We included 309 patients, with a median follow up of 1.87 years (IQR 0.72-3.67). The primary endpoint was more prevalent in CLTI and AI patients (33% and 33.3%) compared to IC patients (8.1%), P<0.001. CLTI and AI were independently associated with the primary endpoint after adjusting for clinical variables of interest (OR 4.04 95%CI [1.86-9.07], P<0.001 and OR 5.40 95%CI [2.18-13.7], P<0.001, respectively). Mortality incidence rate (per 100 patients/year) was similar between AI and CLTI patients (14.2 95% CI [8.0-24.1] and 13.1 95%CI [8.8-19.7], respectively, P=0.67) but higher compared to IC (2.9 95%CI [1.6-5.1], P<0.01). Major amputation events were more prevalent in CLTI (16.5%) compared to AI (8.9%) and IC patients (1.2%), P<0.01. CONCLUSIONS: Those with CLTI and AI have a particular increased risk of all-cause death and major amputation events. Although mortality incidence was similar between AI and CLTI patients, the latter have an increased risk of major amputation events compared to AI and IC patients.

Balloon aortic valvuloplasty through the novel transradial technique.

BACKGROUND: Balloon aortic valvuloplasty (BAV) has been typically performed through a femoral approach thus increasing the risk of bleeding and access site-related vascular complications. The aim of this study was to describe the safety and efficacy of transradial aortic valve valvuloplasty (TRBAV). METHODS: The present research is a retrospective, single-center study including patients undergoing TRBAV (October 2019-July 2020). BAV was performed using 18-25 mm balloons through an 8-10 French (F) radial sheath. Successful BAV was defined as ≥50% reduction in peak-to-peak gradient (efficacy endpoint). Procedural complications, including radial artery occlusion (RAO) at follow-up were evaluated (safety endpoint). RESULTS: Twenty-four patients underwent TRBAV were included, aged 81 (73-85) years, 70% males, EuroScoreII 3.1 (2.1-5.5). Aortic valve gradient was significantly reduced (pre-50±24 vs. 18.7±13 mmHg post, P<0.001), and 91% had successful BAV. Mean gradient drop was 31.4±16.8 mmHg. One patient (4%) required cross-over to femoral access for severe vasospasm and was excluded from the analysis. Most used sheaths were 8F (46%) and 9F (37%), mostly for 20 mm (50%) and 23 mm (38%) balloons. There were neither major procedural complications (neither balloon entrapment nor compartmental syndrome) nor minor complications (any access-site bleeding). RAO was observed in 2 patients (8%), both asymptomatic. CONCLUSIONS: TRBAV was safe, feasible, and efficacious with a small rate of conversion and RAO, suggesting reproducibility of this novel technique. TRBAV may represent an alternative to femoral access in selected patients although larger studies are warranted.

Anterograde and Retrograde Approach With Through-and-Through Wiring Technique to Treat a Ruptured and Extremely Tortuous Giant Popoliteal Artery Aneurism.

PURPOSE: This technical note aims to show a challenging endovascular treatment approach of a giant and tortuous ruptured popliteal artery aneurism. MATERIALS AND METHODS: An 86-year-old male patient was admitted for acute lower right limb ischemia. Angio-MSCT showed highly calcified superficial femoral artery, with a 180° bend in distal portion, followed by a large popliteal aneurism (63 × 61 mm) with a large extent hematoma (142 × 112 × 104 mm). Endovascular approach was chosen due to high morbidity. RESULTS: Anterior puncture of right superficial femoral artery was performed under ultrasound guidance. Despite various intents, the 0.035 hydrophilic coated wire could not be crossed distally through the aneurism. Retrograde access was performed via tibio-peroneal trunk under fluoroscopic guidance with a micropuncture set. A stiff 0.035″ Glidewire® was successfully advanced into the proximal portion of the aneurism through a 5F vertebral catheter externalized with a snare from the femoral sheath obtaining a "through-and-through wire" technique. Tightening of both ends of the wire helped gain support and straightened curves. Two stent grafts were implanted with no residual leak at 1 month follow-up. CONCLUSION: Anterograde and retrograde approach was useful to perform a through-and-through wire technique in a challenging case of a tortuous ruptured popliteal artery aneurism.

Implante valvular aórtico percutáneo por vía transfemoral y apical. Impacto y consideraciones generales de ambos abordajes / Transapical and Transfemoral Aortic Valve Implantation. Impact and General Considerations of both Approaches

RESUMEN: Introducción: La miectomía septal ampliada constituye el tratamiento de elección para pacientes con miocardiopatía hipertrófica obstructiva sintomática, refractarios al tratamiento farmacológico. Objetivos: Evaluar los resultados posoperatorios, el cambio en los síntomas y la evolución ecocardiográfica de una población sometida a miectomía septal ampliada por miocardiopatía hipertrófica obstructiva sintomática. Material y métodos: Desde noviembre de 2011 a octubre de 2017, se intervino un total de 28 pacientes. Se analizaron la evolución posoperatoria, clínica y ecocardiográfica al alta y al seguimiento. Resultados: Edad promedio 53,3 ± 13,4 años. La mortalidad perioperatoria (< 30 días) fue del 0%. Un paciente falleció a los 90 días (3,5%). No se produjeron comunicaciones interventriculares, daño de la válvula aórtica ni se reemplazó la válvula mitral en ningún paciente. El 91% de ellos se encontraban con disnea en CF III-IV en el preoperatorio, los restantes tenían angina o síncope. En el seguimiento, el 92,8% estaban asintomáticos, 1 paciente en CF III y otro en CF II. El gradiente preoperatorio basal promedio fue de 53,5 mmHg y con valsalva 86,4 mmHg; los gradientes basal y con valsalva posoperatorios fueron 9,4 mmHg y 13,5 mmHg (p < 0,01). Al seguimiento, los gradientes en reposo y con valsalva fueron aún más bajos, 8,3 mmHg y 10,7 mmHg, respectivamente (p: NS). Nueve pacientes (32%) presentaban insuficiencia mitral moderada a grave previa por movimiento anterior sistólico o patología intrínseca mitral. Se detectó solo un paciente con insuficiencia mitral moderada asintomática en el seguimiento (3,5%). La mediana de seguimiento fue de 400 días, Pc 25-75 de 695 días (mínimo de 30 días y el máximo de 1868 días). Conclusión: Con la miectomía septal ampliada se obtiene una mejoría hemodinámica y clínica de los pacientes sintomáticos, con bajo número de complicaciones posoperatorias. Esto tiene como resultado una mejor calidad de vida.

Restenosis, Stent Thrombosis, and Bleeding Complications: Navigating Between Scylla and Charybdis.

The field of interventional cardiology has significantly evolved over 40 years by overcoming several challenges. The introduction of first-generation drug-eluting stents significantly reduced the rates of restenosis, but at the expense of an increase of late stent thrombosis. Prolonged antithrombotic therapy reduced rates of stent thrombosis, but at the cost of increased bleeding. Although the advent of second-generation drug-eluting stents subsequently reduced the incidence of late stent thrombosis, its permanent nature prevents full recovery of vascular structure and function with accordant risk of very late stent failure. In the present era of interventional cardiology, the tradeoff between stent thrombosis, restenosis, and bleeding presents as a particularly complex challenge. In this review, the authors highlight major contributors of late/very late stent thrombosis while targeting stent restenosis, and they discuss evolutionary advances in stent technology and antiplatelet therapy, to further improve upon the care of patients with coronary artery disease.

Reperfusion therapy with recombinant human relaxin-2 (Serelaxin) attenuates myocardial infarct size and NLRP3 inflammasome following ischemia/reperfusion injury via eNOS-dependent mechanism.

AIMS: The preconditioning-like infarct-sparing and anti-inflammatory effects of the peptide hormone relaxin following ischemic injury have been studied in the heart. Whether reperfusion therapy with recombinant human relaxin-2, serelaxin, reduces myocardial infarct size and attenuates the subsequent NLRP3 inflammasome activation leading to further loss of functional myocardium following ischemia/reperfusion (I/R) injury is unknown. METHODS AND RESULTS: After baseline echocardiography, adult male wild-type C57BL or eNOS knockout mice underwent myocardial infarction (MI) by coronary artery ligation for 30 min followed by 24 h reperfusion. Mice were treated with either serelaxin (10 µg/kg; sc) or saline 1 h prior to ischemia or 5 min before reperfusion. In both pre-treatment and reperfusion therapy arms, serelaxin improved survival at 24 h post MI in wild-type mice (79% and 82%) as compared with controls (46% and 50%, P = 0.01), whereas there was no difference in survival between serelaxin- and saline-treated eNOS knockout mice. Moreover, serelaxin significantly reduced infarct size (64% and 67% reduction, P < 0.05), measured with TTC staining, and preserved LV fractional shortening (FS) and end-systolic diameter (LVESD) in wild-type mice as compared with controls (P < 0.05). Interestingly, caspase-1 activity in the heart tissue, a measure of inflammasome formation, was markedly reduced in serelaxin-treated wild-type mice compared with controls at 24 h post-MI in both treatment modalities (P < 0.05). Genetic deletion of eNOS abolished the infarct-sparing and anti-inflammatory effects of serelaxin as well as functional preservation. Serelaxin plasma levels assessed at 5 min and 1 h after treatment, using ELISA, approximated physiologic relaxin levels during pregnancy in mice and parallels that in humans. CONCLUSION: Serelaxin attenuates myocardial I/R injury and the subsequent caspase-1 activation via eNOS-dependent mechanism.

A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome of HF symptoms associated with impaired diastolic function. Although it represents ∼50% of patients with HF, the mechanisms of disease are poorly understood, and therapies are generally ineffective in reducing HF progression. Animal models of HFpEF not due to pressure or volume overload are lacking, therefore limiting in-depth understanding of the pathophysiological mechanisms and the development of novel therapies. We hypothesize that a continuous infusion of low-dose angiotensin II (ATII) is sufficient to induce left ventricular (LV) diastolic dysfunction and HFpEF, without increasing blood pressure or inducing LV hypertrophy or dilatation. Osmotic pumps were implanted subcutaneously in 8-wk-old male mice assigned to the ATII (0.2 mg·kg(-1)·day(-1)) or volume-matched vehicle (N = 8/group) for 4 wk. We measured systolic and diastolic arterial blood pressures through a tail-cuff transducer, LV dimensions and ejection fraction through echocardiography, and LV relaxation through pulsed-wave Doppler and LV catheterization. Myocardial fibrosis and cardiomyocyte cross-sectional area were measured. ATII infusion had no effects on systemic arterial blood pressure. ATII induced significant impairment in LV diastolic function, as measured by an increase (worsening) in LV isovolumetric relaxation time, myocardial performance index, isovolumetric relaxation time constant, and LV end-diastolic pressure without altering LV dimensions, mass, or ejection fraction. Chronic infusion of low-dose ATII recapitulates the HFpEF phenotype in the mouse, without increasing systemic arterial blood pressure. This mouse model may provide insight into the mechanisms of HFpEF.

Diagnóstico etiológico de la miocardiopatía en pacientes receptores de trasplante cardíaco: Concordancia entre el diagnóstico clínico pretrasplante y la anatomía patológica / Etiologic Diagnosis of Cardiomyopathy in Heart Transplant Recipients: Agreement Between Pre-transplant Clinical Diagnosis and Pathology

Introducción: El diagnóstico etiológico en pacientes con miocardiopatías en estadio avanzado puede ser un desafío. Un gran número de pacientes permanecen sin diagnóstico a pesar de una evaluación exhaustiva, por lo que quedan rotuladas como miocardiopatías dilatadas idiopáticas. Objetivos: Describir la etiología de la miocardiopatía en pacientes receptores de trasplante cardíaco según el diagnóstico clínico pretrasplante y su grado de concordancia con el diagnóstico anatomopatológico del corazón explantado. Material y métodos: Se realizó un análisis retrospectivo de pacientes consecutivos trasplantados en un hospital de alta complejidad de la Ciudad Autónoma de Buenos Aires desde 2003 hasta fines de 2013. Se efectuó un análisis de concordancia entre el diagnóstico clínico pretrasplante y el diagnóstico anatomopatológico del corazón explantado utilizando el coeficiente kappa. Resultados: Se analizaron 100 pacientes con una edad media en el momento del trasplante de 49,7 ± 12,5 años y una mediana de fracción de eyección del 26,6%. El diagnóstico clínico pretrasplante más frecuente fue el de miocardiopatía dilatada idiopática (37%), seguida por la miocardiopatía isquémico-necrótica (32%) y la miocardiopatía chagásica (10%). Entre los diagnósticos histopatológicos más frecuentes se encontraron el de miocardiopatía isquémico-necrótica (35%), de miocardiopatía hipertrófica (10%), de miocardiopatía chagásica (10%) y de miocarditis (8%); no se arribó a un diagnóstico causal en el 25% (miocardiopatía dilatada idiopática). El resultado del coeficiente kappa fue de 0,64 (IC 0,52-0,76). Conclusiones: Aproximadamente un tercio de los pacientes llegan al trasplante sin un diagnóstico etiológico. El análisis anatomopatológico permite identificar la causa en más de la mitad de estos pacientes. A pesar de que la concordancia entre el diagnóstico pretrasplante y la anatomía patológica fue estadísticamente buena, un porcentaje importante de pacientes podría beneficiarse con un diagnóstico etiológico más preciso, que podría tener implicaciones pronósticas, terapéuticas y/o en la evaluación de familiares.

Introduction: Etiologic diagnosis in patients with end-stage cardiomyopathy can be challenging. A large number of patients remain undiagnosed despite a thorough evaluation, so they are classified as idiopathic dilated cardiomyopathies. Objectives: To describe the etiology of cardiomyopathy in heart transplant recipients according to pretransplant clinical diagnosis and its degree of agreement with the anatomopathological diagnosis of the explanted heart. Methods: We performed a retrospective analysis of consecutively transplanted patients in a high complexity hospital of the Autonomous City of Buenos Aires from 2003 to the end of 2013. An agreement analysis between pretransplantation clinical diagnosis and anatomopathological diagnosis of the explanted heart was done using the kappa coefficient. Results: One-hundred patients with mean age of 49.7 ± 12.5 years at the time of transplantation and median ejection fraction of 26.6% were analyzed. The most common pretransplant clinical diagnosis was idiopathic dilated cardiomyopathy (37%), followed by ischemic-necrotic cardiomyopathy (32%) and Chagas cardiomyopathy (10%). The most common histopathological diagnoses were ischemic-necrotic cardiomyopathy (35%), hypertrophic cardiomyopathy (10%), Chagas cardiomyopathy (10%) and myocarditis (8%); a causal diagnosis was not reached in 25% of cases (idiopathic dilated cardiomyopathy). The kappa coefficient was 0.64 (CI 0.52-0.76). Conclusions: Approximately one third of patients reach transplantation without an etiologic diagnosis. Anatomopathological analysis allows identifying the cause in more than half of these patients. Although the correlation between pretransplant diagnosis and pathological anatomy was statistically adequate, a significant percentage of patients could benefit from a more specific etiologic diagnosis, which may have prognostic, therapeutic and/or family assessment implications.

Diagnóstico etiológico de la miocardiopatía en pacientes receptores de trasplante cardíaco: Concordancia entre el diagnóstico clínico pretrasplante y la anatomía patológica / Etiologic Diagnosis of Cardiomyopathy in Heart Transplant Recipients: Agreement Between Pre-transplant Clinical Diagnosis and Pathology

Introducción: El diagnóstico etiológico en pacientes con miocardiopatías en estadio avanzado puede ser un desafío. Un gran número de pacientes permanecen sin diagnóstico a pesar de una evaluación exhaustiva, por lo que quedan rotuladas como miocardiopatías dilatadas idiopáticas. Objetivos: Describir la etiología de la miocardiopatía en pacientes receptores de trasplante cardíaco según el diagnóstico clínico pretrasplante y su grado de concordancia con el diagnóstico anatomopatológico del corazón explantado. Material y métodos: Se realizó un análisis retrospectivo de pacientes consecutivos trasplantados en un hospital de alta complejidad de la Ciudad Autónoma de Buenos Aires desde 2003 hasta fines de 2013. Se efectuó un análisis de concordancia entre el diagnóstico clínico pretrasplante y el diagnóstico anatomopatológico del corazón explantado utilizando el coeficiente kappa. Resultados: Se analizaron 100 pacientes con una edad media en el momento del trasplante de 49,7 ± 12,5 años y una mediana de fracción de eyección del 26,6%. El diagnóstico clínico pretrasplante más frecuente fue el de miocardiopatía dilatada idiopática (37%), seguida por la miocardiopatía isquémico-necrótica (32%) y la miocardiopatía chagásica (10%). Entre los diagnósticos histopatológicos más frecuentes se encontraron el de miocardiopatía isquémico-necrótica (35%), de miocardiopatía hipertrófica (10%), de miocardiopatía chagásica (10%) y de miocarditis (8%); no se arribó a un diagnóstico causal en el 25% (miocardiopatía dilatada idiopática). El resultado del coeficiente kappa fue de 0,64 (IC 0,52-0,76). Conclusiones: Aproximadamente un tercio de los pacientes llegan al trasplante sin un diagnóstico etiológico. El análisis anatomopatológico permite identificar la causa en más de la mitad de estos pacientes. A pesar de que la concordancia entre el diagnóstico pretrasplante y la anatomía patológica fue estadísticamente buena, un porcentaje importante de pacientes podría beneficiarse con un diagnóstico etiológico más preciso, que podría tener implicaciones pronósticas, terapéuticas y/o en la evaluación de familiares.(AU)

Introduction: Etiologic diagnosis in patients with end-stage cardiomyopathy can be challenging. A large number of patients remain undiagnosed despite a thorough evaluation, so they are classified as idiopathic dilated cardiomyopathies. Objectives: To describe the etiology of cardiomyopathy in heart transplant recipients according to pretransplant clinical diagnosis and its degree of agreement with the anatomopathological diagnosis of the explanted heart. Methods: We performed a retrospective analysis of consecutively transplanted patients in a high complexity hospital of the Autonomous City of Buenos Aires from 2003 to the end of 2013. An agreement analysis between pretransplantation clinical diagnosis and anatomopathological diagnosis of the explanted heart was done using the kappa coefficient. Results: One-hundred patients with mean age of 49.7 ± 12.5 years at the time of transplantation and median ejection fraction of 26.6% were analyzed. The most common pretransplant clinical diagnosis was idiopathic dilated cardiomyopathy (37%), followed by ischemic-necrotic cardiomyopathy (32%) and Chagas cardiomyopathy (10%). The most common histopathological diagnoses were ischemic-necrotic cardiomyopathy (35%), hypertrophic cardiomyopathy (10%), Chagas cardiomyopathy (10%) and myocarditis (8%); a causal diagnosis was not reached in 25% of cases (idiopathic dilated cardiomyopathy). The kappa coefficient was 0.64 (CI 0.52-0.76). Conclusions: Approximately one third of patients reach transplantation without an etiologic diagnosis. Anatomopathological analysis allows identifying the cause in more than half of these patients. Although the correlation between pretransplant diagnosis and pathological anatomy was statistically adequate, a significant percentage of patients could benefit from a more specific etiologic diagnosis, which may have prognostic, therapeutic and/or family assessment implications.(AU)