Risk stratification, prognosis, and survival in a pulmonary arterial hypertension cohort in Latin America. A multicenter study.

BACKGROUND: Pulmonary arterial hypertension (PAH) guidelines suggest that achieving a low-risk profile should be the treatment goal. Our aim was to assess a risk assessment strategy based on three non-invasive variables from the ESC/ERS 2015 guidelines in a Latin American cohort. METHODS: 92 incident patients (mean [SD] age 47, 77% female, 53% idiopathic PAH) were included in this retrospective, multicenter study. Patients were stratified at baseline and at early follow-up, within the first year, using three non-invasive variables (WHO functional class, 6-minute walking distance, BNP/NT-proBNP) from the ESC/ERS 2015 risk assessment instrument. Median (IQR) follow-up was 3.11 years (3.01 years). RESULTS: At baseline assessment, 25% of patients were at low risk, 61.9% at intermediate-risk, and 13% at high-risk. At early follow-up (median 9.5 months), 56.5% of patients were at low-risk, 40.2% at intermediate-risk, and 3.2% at high-risk (p<0.001 vs. baseline). According to risk stratification at early follow-up, one, three and five-year overall survival was 100% in the low-risk group (no deaths at five-year follow-up), and 100%, 84% (95% CI: 72-98%), and 66% (95% CI: 48-90%) respectively in the intermediate-risk group, p = 0.0003. Mortality in the high-risk patients at early follow-up was 1/3 (33.3%). One, three, and five-year event-free survival (death or transplant or first hospitalization due to worsening PAH) based on early follow-up risk assessment was higher in the low-risk group, p = 0.0003. CONCLUSION: Our study validates a risk assessment strategy based on three non-invasive variables and confirms that early achievement of a low-risk profile should be the treatment goal.

Terapia de resincronización cardíaca. Incidencia y mecanismos involucrados en la reducción de la insuficiencia mitral funcional / Cardiac Resynchronization Therapy. Incidence and Mechanisms Involved in the Reduction of Functional Mitral Regurgitation

RESUMEN Introducción: La insuficiencia mitral funcional (IMF) es común en pacientes con insuficiencia cardíaca (IC). La IMF moderada/ grave (M/G) se asocia a peor pronóstico. Objetivo: Describir la prevalencia de IMF y los mecanismos involucrados en su reducción en respondedores a la terapia de resincronización cardíaca (TRC) a los 6 meses comparados con 12 y 24 meses. Métodos: Entre 2009 y 2018 fueron tratados 338 pts. Respondedores: reducción de CF NYHA ≥1 grado o aumento de la fracción de eyección ventricular izquierda (FEVI) ≥5% (absoluto). La IMF se graduó en 4 puntos: No-IMF, leve, M y G, y se la relacionó con las mediciones ecocardiográficas. Características Basales: edad 64 ±10 años, hombres 71%, CF-NYHA IIIII 92%, bloqueo de rama izquierda (BRI) 67%, QRS ≥150 ms 75%, diámetro diastólico del VI (DDVI) 68 ± 9 mm, diámetro sistólico del VI (DSVI) 52 ± 12 mm, FEVI 24 ± 7%. Resultados: La prevalencia de IMF fue del 92,6%. A los 6 meses, 86% fueron respondedores y 23% de ellos mejoraron de IMF-M/G a IMF-Leve/No-IMF. Hubo un fuerte remodelado inverso: DDVI 68 ± 10 vs 63 ± 11 mm, (p = 0,0001), DSVI 55 ± 12 vs 50 ± 13 mm, (p = 0,0006) y FEVI 25 ± 11 vs 33 ± 10%, (p = 0,00001). Comparando 6 con 12 meses 89,4% fueron respondedores, 8% mejoraron de IMF-M/G a IMF-Leve/No-IMF. Comparando 6 con 24 meses 88% fueron respondedores, 14,6% mejoraron de IMF-M/G a IMF-Leve/No-IMF. Entre 6 y 12 y 6 y 24 meses no hubo remodelado inverso significativo. Conclusiones: La prevalencia de IMF fue elevada. El mayor remodelado inverso y reducción de la IMF se observaron a los 6 meses, siendo el primero el principal mecanismo en la reducción de la IMF. Esta mejoría se sostuvo a los 12 y 24 meses.

ABSTRACT Background: Functional mitral regurgitation (FMR) is common in heart failure, and moderate/severe (M/S) FMR is associated with worse prognosis. Objective: The aim of this study was to describe the prevalence of FMR and the mechanisms involved in its reduction in responders to cardiac resynchronization therapy (CRT) at 6 months compared with 12 and 24 months. Methods: Between 2009 and 2018, 338 patients received CRT. Patients showing NYHA functional class (FC) reduction ≥1 or left ventricular ejection fraction (LVEF) absolute increase ≥5% were considered responders. Functional mitral regurgitation was graded using a 4-point scale into none-, mild-, M- and S-FMR, and was related to echocardiographic measurements. Baseline patient characteristics were: age 64±10 years, men 71%, NYHA FC II-III 92%, left bundle branch block (LBBB) 67%, QRS ≥150 ms 75%, LV diastolic diameter (LVDD) 68±9 mm, LV systolic diameter (LVSD) 52±12 mm, and LVEF 24±7%. Results: The prevalence of FMR was 92.6%. At 6 months, 86% were responders, 23% improved from M/S-FMR to mild/none-FMR and there was strong reverse remodeling: LVDD 68±10 vs. 63±11 mm, (p=0.0001), LVSD 55±12 vs. 50±13 mm, (p=0.0006) and LVEF 25±11 vs. 33±10%, (p=0.00001). Comparing 6 with 12 months, 89.4% were responders and 8% improved M/S-FMR to mild/none-FMR. Comparing 6 with 24 months, 88% were responders and 14.6% improved M/S-FMR to mild/none-FMR. Between 6 and 12 and 6 and 24 months, there was no significant reverse remodeling. Conclusions: The prevalence of FMR was high. The highest reverse remodeling and FMR reduction was observed at 6 months, the former being the main mechanism of FMR reduction. This improvement persisted at 12 and 24 months.

Trasplante cardíaco en miocardiopatía chagásica: 23 años de experiencia en un centro de referencia / Heart Transplantation in Chagas Cardiomyopathy: 23-Year Follow-Up in a Referral Center

RESUMEN Introducción: La enfermedad de Chagas afecta aproximadamente a 6 millones de personas en América Latina. El 25 a 35% evoluciona hacia la Miocardiopatía Chagásica (MCh). Una opción terapéutica en sus estadios avanzados es el trasplante cardíaco (TxC). Objetivos: Comparar la supervivencia de pacientes con TxC por MCh frente a otras etiologías. Analizar la incidencia de la reactivación (Ra) de enfermedad de Chagas y su impacto en la supervivencia en este subgrupo de pacientes. Material y métodos: Se evaluaron retrospectivamente pacientes con TxC entre agosto 1998 y marzo 2021. Se analizó la supervivencia mediante curvas de Kaplan-Meier y log rank test. El diagnóstico de Ra se realizó mediante métodos moleculares, prueba de Strout en sangre periférica, tejido miocárdico y/o cutáneo. Resultados: De 606 pacientes con TxC, 39 (6,4%) presentaban MCh. Seguimiento medio 4,4 años (Rango Intercuartilo 1,2-8,6). Edad subgrupo MCh 51 años (RIC 45-60). Hombres 28 (72%). Se documentó Ra en el 38,5% de los pacientes. Supervivencia a 1, 5 y 10 años en TxC por MCh con Ra versus no Ra: 85%, 76% y 61% versus 72%, 55% y 44% (p = 0,3). Supervivencia a 1, 5 y 10 años en TxC por MCh versus TxC por otras causas: 79%, 65% y 50% versus 79%, 62% y 47% (p = 0,5). Conclusión: En nuestra serie no se encontró diferencia estadísticamente significativa en la supervivencia de los pacientes trasplantados cardíacos por MCh en comparación con aquellos trasplantados por otras causas; así como tampoco entre los pacientes que reactivaron la enfermedad de Chagas y los que no lo hicieron.

ABSTRACT Background: Chagas disease affects about 6 million people in Latin America, and 25 to 35% progress to Chagas cardiomyopathy (ChCM). Heart transplantation (HTx) is a therapeutic option in advanced stages. Objectives: The aim of this study is to compare survival of patients with HTx due to ChCM versus those transplanted for other etiologies and to analyze the incidence of Chagas disease reactivation (Ra) and its impact on survival in this group of patients. Methods: Patients undergoing HTx between August 1998 and March 2021 were retrospectively evaluated. Survival was analyzed using Kaplan-Meier curves and the log-rank test. The diagnosis of Ra was performed by molecular methods, Strout's test in peripheral blood, myocardial tissue or skin tissue. Results: Of 606 patients with Htx, 39(6,4%) presented ChCM. Median follow up was 4.4 years (interquartile range 1.2-8.6). Median age of the subgroup with ChCM was 51 years (IQR 45-60) and 28 were men (72%). Reactivation was documented in 38.5% of the patients. Survival at 1, 5 and 10 years in HTx recipients due to ChCM and Ra versus no Ra was 85%, 76% and 61% versus 72%, 55% and 44%, respectively (p = 0.3). Survival at 1, 5 and 10 years in HTx recipients due to ChCM versus HTx for other causes was 79%, 65% and 50% versus 79%, 62% and 47%, respectively (p = 0.5). Conclusion: In our series we did not find statistically significant differences in survival of heart transplant recipients due to ChCM versus those transplanted due to other reasons. Survival in patients with Chagas disease reactivation and those without reactivation was also similar.

Hospital de día en la unidad de insuficiencia cardíaca como una estrategia de abordaje integral: análisis de un único centro en América Latina / Heart Failure Day Hospital as a Comprehensive Approach Strategy in the Heart Failure Unit: Analysis of a Single Center in Latin America

RESUMEN Objetivos: Describir las características clínicas, el impacto en la calidad de vida, la clase funcional (CF), el número de internaciones y la supervivencia de los pacientes que ingresaron a un hospital de día (HD) de insuficiencia cardíaca (IC). Material y métodos: Se analizaron en forma retrospectiva aquellos pacientes que ingresaron a un HD para la infusión de hierro, furosemida, levosimendán o la combinación de estos dos últimos fármacos, durante un período de 3 años. Las variables analizadas, al inicio y a los 6 meses, fueron la CF (NYHA), la prueba de marcha de 6 minutos (PM6M) y calidad de vida mediante el cuestionario de Minnesota (MLHFQ). El número de internaciones por IC fue comparado con el del año previo al ingreso al HD y la supervivencia fue evaluada al año de seguimiento. Resultados: Se observó una mejoría significativa de la CF en los 4 grupos, y del número de internaciones por IC en los primeros 3. Conclusiones: El desarrollo del HD puede modificar el presente y futuro de esta población.

ABSTRACT Objectives: To describe the clinical characteristics, impact on quality of life, functional class (FC), number of hospitalizations, and survival rate of patients with heart failure (HF) enrolled in an outpatient heart failure clinic (HFC). Methods: Patients enrolled in a HFC for infusion of iron, furosemide, levosimendan -or the combination of these two drugsover a 3-year period were retrospectively analyzed. Baseline and 6-month variables were FC (NYHA), 6-minute walk test (6MWT) and quality of life using the Minnesota questionnaire (MLHFQ). The number of HF hospitalizations was compared with that of the year prior to HFC enrollment, and survival was assessed at 1-year follow-up. Results: A significant improvement in FC was observed in all four groups, and a decrease of HF hospitalizations in the first three. Conclusions: Outpatient HFC development can change the present and future of this population.

Primer implante exitoso de asistencia ventricular izquierda HeartMate 3TM como terapia de destino en Argentina. Revisión de la literatura / First successful Heartmate 3TM left ventricular assist device implantation as destination therapy in Argentina

RESUMEN Se presenta el primer implante exitoso de asistencia ventricular izquierda como terapia de destino mediante el dispositivo de flujo continuo centrífugo con levitación magnética intracorpóreo HeartMate 3TM (Abbott) en la Argentina. El dispositivo se implantó en una paciente de 52 años portadora de miocardio no compacto con disfunción ventricular izquierda grave, hipertensión pulmonar, insuficiencia cardíaca avanzada en estadio INTERMACS 3 y contraindicación para trasplante cardíaco debido a títulos elevados de anticuerpos preformados contra el sistema HLA en crossmatch contra panel.

ABSTRACT First case of successful implantation of intracorporeal full magnetically levitated continuous centrifugal flow left ventricular assist device HeartMate 3 Abbott® as destination therapy in Argentina in a female patient, 52-years-old with non compaction cardiomyopathy, severe left ventricular dysfunction, pulmonary hypertension, end-stage heart failure INTERMACS 3 and contraindication for heart transplantation due to high titers of preformed antibodies against the HLA system in panel reactive antibody assay.

Heart Failure and Diabetes: Perspective of a Dangerous Association.

The relationship between diabetes and risk of heart failure has been described in previous trials, releasing the importance of the hyperglycemic state that, added to other risk factors, favors the development of coronary heart disease. The mechanism by which, in the absence of hypertension, obesity and/or dyslipidemia, diabetic patients develop cardiomyopathy has been less studied. Recently, the Sodium Glucose Co-transporter type 2 inhibitors (SGLT2 inhibitors) used for the treatment of heart failure patients with or without diabetes has been a breakthrough in the field of medicine. This review describes the established pathophysiology of diabetic cardiomyopathy and SGLT2 inhibitors, their mechanisms of action, and benefits in this group of patients.

Intravascular ultrasound for cardiac allograft vasculopathy detection.

Cardiac allograft vasculopathy (CAV) after heart transplantation is a fibro-proliferative process affecting coronary arteries of the graft in up to 46.8% of the cases during the first 10 years post-transplantation. It is one of the main causes of graft loss and death. Due to graft denervation, CAV causing ischemia is usually clinically silent until the disease is far advanced. In this study, we compared coronary angiography with intravascular ultrasound (IVUS) for CAV detection. OUTCOMES: A total of 114 patients with HTx who underwent coronary angiography and IVUS between March 2018 and March 2019 were included. Mean follow-up was 87 ± 61 month. Lesions documented by coronary angiography were found in only 27 (24%) of the 114 patients. IVUS revealed ISHLT CAV 0 in 87 patients (76.3%); ISHLT CAV1 in 15 (13,1%) and ISHLT CAV2 and CAV3 in 6 patients (5.2%) each. Among 328 IVUS images, maximum intimal thickness (MIT) >0.5 mm was obtained in 60 vessels (52%) with 24 patients having three-vessel and 19 two-vessel involvement. CONCLUSION: As an adjunct to conventional coronary angiography to detect angiographically silent CAV in heart transplant patients, IVUS is a reliable and safe technique with a low complication rate. Large multicenter studies are necessary to confirm these findings and the potential long-term clinical impact of early detection in clinically and angiographically silent phase.

Radiofrequency ablation of supraventricular arrhythmias after orthotopic heart transplantation: Long-term follow-up of a single-center experience.

BACKGROUND: Supraventricular arrhythmias (SVAs), commonly managed with radiofrequency ablation (RFA), may occur after orthotopic heart transplantation (OHT). METHODS: We retrospectively assessed 514 consecutive patients (pts.) undergoing OHT between January 1990 and July 2016 in a single-center. Patients with SVAs managed with RFA were included. Mechanisms of genesis of SVAs, association with surgical techniques and outcomes, were analyzed. RESULTS: Of 514 pts undergoing OHT, 53% (272 pts.) were managed with bicaval (BC) technique and 47% (242 pts.) with biatrial (BA) technique. Mean follow-up 10 ± 8.4 years. Nine pts. (1.7%) developed SVA requiring RFA. The BC technique was performed in 4 pts., 3 pts. presented cavotricuspid isthmus-dependent atrial flutter (CTI AFL), and 1 pt. double loop AFL. Five pts. were managed with BA technique, 4 pts. presented CTI AFL, and 1 pt. atrial tachycardia (AT). Mean time between OHT and SVA occurrence was 6.6 ± 5.5 years. The procedure was successful in 89% (8 pts.). Arrhythmia recurrence was seen in 3 pts (37%), all with BA technique. CONCLUSION: Supraventricular arrhythmias in heart transplantation may be associated with the surgical scar. Identifying the mechanism is vital to choose the appropriate treatment with radiofrequency ablation.

Dynamic neurocognitive changes in interoception after heart transplant.

Heart-brain integration dynamics are critical for interoception (i.e. the sensing of body signals). In this unprecedented longitudinal study, we assessed neurocognitive markers of interoception in patients who underwent orthotopic heart transplants and matched healthy controls. Patients were assessed longitudinally before surgery (T1), a few months later (T2) and a year after (T3). We assessed behavioural (heartbeat detection) and electrophysiological (heartbeat evoked potential) markers of interoception. Heartbeat detection task revealed that pre-surgery (T1) interoception was similar between patients and controls. However, patients were outperformed by controls after heart transplant (T2), but no such differences were observed in the follow-up analysis (T3). Neurophysiologically, although heartbeat evoked potential analyses revealed no differences between groups before the surgery (T1), reduced amplitudes of this event-related potential were found for the patients in the two post-transplant stages (T2, T3). All these significant effects persisted after covariation with different cardiological measures. In sum, this study brings new insights into the adaptive properties of brain-heart pathways.

Short-term mechanical circulatory support devices as bridge to heart transplantation: A prospective single-center experience in Argentina.

BACKGROUND: Patients with cardiogenic shock may require hemodynamic stabilization with short-term mechanical circulatory support devices (ST-MCS) such as extracorporeal membrane oxygenation (ECMO) and centrifugal pump (CP) as bridge to transplantion (BTT). This study aimed to describe ECMO and CP during BTT and after heart transplant. METHODS: A cohort of patients on ECMO or CP as BTT between April 2006 and April 2018 in a single hospital. RESULTS: Thirty-seven consecutive patients with ECMO (n = 14) or CP (n = 23) were included. Acute kidney injury was more prevalent during CP (28.6% vs 69.6%, P = .02). There were no differences in stroke, thrombosis, sepsis, or vasoplegia. Bleeding (0% vs 56.5%, P = .0003) and reoperation (0% vs 47.8%, P = .002) were more frequent in CP group as well as mortality (0 vs 7 [30.4%], P = .03). The remaining 30 patients (81.1%) underwent heart transplantation, without differences in primary graft dysfunction, vasoplegia, reoperation for bleeding, or hospital stay. Mortality was 23.3% at 30 days, similar in both groups, with no further deaths at median follow-up of 44.2 months. CONCLUSIONS: In patients with cardiogenic shock, ST-MCS with ECMO or CP as BTT are a lifesaving approach allowing successful transplantation in the majority of cases, with good short- and long-term survival.

Myocardial Viability and Long-Term Outcomes in Ischemic Cardiomyopathy.

BACKGROUND: The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear. METHODS: Among 601 patients who had coronary artery disease that was amenable to coronary-artery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photon-emission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years. RESULTS: CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P = 0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death. CONCLUSIONS: The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.).

Myocardial viability and long-term outcomes in ischemic cardiomyopathy

BACKGROUND: The role of assessment of myocardial viability in identifying patients with ischemic cardiomyopathy who might benefit from surgical revascularization remains controversial. Furthermore, although improvement in left ventricular function is one of the goals of revascularization, its relationship to subsequent outcomes is unclear. METHODS: Among 601 patients who had coronary artery disease that was amenable to coronaryartery bypass grafting (CABG) and who had a left ventricular ejection fraction of 35% or lower, we prospectively assessed myocardial viability using single-photonemission computed tomography, dobutamine echocardiography, or both. Patients were randomly assigned to undergo CABG and receive medical therapy or to receive medical therapy alone. Left ventricular ejection fraction was measured at baseline and after 4 months of follow-up in 318 patients. The primary end point was death from any cause. The median duration of follow-up was 10.4 years. RESULTS: CABG plus medical therapy was associated with a lower incidence of death from any cause than medical therapy alone (182 deaths among 298 patients in the CABG group vs. 209 deaths among 303 patients in the medical-therapy group; adjusted hazard ratio, 0.73; 95% confidence interval, 0.60 to 0.90). However, no significant interaction was observed between the presence or absence of myocardial viability and the beneficial effect of CABG plus medical therapy over medical therapy alone (P=0.34 for interaction). An increase in left ventricular ejection fraction was observed only among patients with myocardial viability, irrespective of treatment assignment. There was no association between changes in left ventricular ejection fraction and subsequent death. CONCLUSIONS: The findings of this study do not support the concept that myocardial viability is associated with a long-term benefit of CABG in patients with ischemic cardiomyopathy. The presence of viable myocardium was associated with improvement in left ventricular systolic function, irrespective of treatment, but such improvement was not related to long-term survival. (Funded by the National Institutes of Health; STICH ClinicalTrials.gov number, NCT00023595.). (AU)

The association between blood pressure and long-term outcomes of patients with ischaemic cardiomyopathy with and without surgical revascularization: an analysis of the STICH trial.

Aims: Hypertension (HTN) is a well-known contributor to cardiovascular disease, including heart failure (HF) and coronary artery disease, and is the leading risk factor for premature death world-wide. A J- or U-shaped relationship has been suggested between blood pressure (BP) and clinical outcomes in different studies. However, there is little information about the significance of BP on the outcomes of patients with coronary artery disease and left ventricular dysfunction. This study aimed to determine the relationship between BP and mortality outcomes in patients with ischaemic cardiomyopathy. Methods and results: The influence of BP during a median follow-up of 9.8 years was studied in a total of 1212 patients with ejection fraction ≤35% and coronary disease amenable to coronary artery bypass grafting (CABG) who were randomized to CABG or medical therapy alone (MED) in the STICH (Surgical Treatment for Ischaemic Heart Failure) trial. Landmark analyses were performed starting at 1, 2, 3, 4, and 5 years after randomization, in which previous systolic BP values were averaged and related to subsequent mortality through the end of follow-up with a median of 9.8 years. Neither a previous history of HTN nor baseline BP had any significant influence on long-term mortality outcomes, nor did they have a significant interaction with MED or CABG treatment. The landmark analyses showed a progressive U-shaped relationship that became strongest at 5 years (χ2 and P-values: 7.08, P = 0.069; 8.72, P = 0.033; 9.86; P = 0.020; 8.31, P = 0.040; 14.52, P = 0.002; at 1, 2, 3, 4, and 5-year landmark analyses, respectively). The relationship between diastolic BP (DBP) and outcomes was similar. The most favourable outcomes were observed in the SBP range 120-130, and DBP 75-85 mmHg, whereas lower and higher BP were associated with worse outcomes. There were no differences in BP-lowering medications between groups. Conclusion: A strong U-shaped relationship between BP and mortality outcomes was evident in ischaemic HF patients. The results imply that the optimal SBP might be in the range 120-130 mmHg after intervention, and possibly be subject to pharmacologic action regarding high BP. Further, low BP was a marker of poor outcomes that might require other interactions and treatment strategies. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Sex Difference in Patients With Ischemic Heart Failure Undergoing Surgical Revascularization: Results From the STICH Trial (Surgical Treatment for Ischemic Heart Failure).

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular dysfunction enrolled in the prospective STICH trial (Surgical Treatment for Ischemic Heart Failure Study). METHODS: The STICH trial randomized 1212 patients (148 [12%] women and 1064 [88%] men) with coronary artery disease and left ventricular ejection fraction ≤35% to CABG+medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 versus 59.3 years; P=0.016) with higher body mass index (27.9 versus 26.7 kg/m2; P=0.001). Women had more coronary artery disease risk factors (diabetes mellitus, 55.4% versus 37.2%; hypertension, 70.9% versus 58.6%; hyperlipidemia, 70.3% versus 58.9%) except for smoking (13.5% versus 21.8%) and had lower rates of prior CABG (0% versus 3.4%; all P<0.05) than men. Moreover, women had higher New York Heart Association class (class III/IV, 66.2% versus 57.0%), lower 6-minute walk capacity (300 versus 350 m), and lower Kansas City Cardiomyopathy Questionnaire overall summary scores (51 versus 63; all P<0.05). Over 10 years of follow-up, all-cause mortality (49.0% versus 65.8%; adjusted hazard ratio, 0.67; 95% confidence interval, 0.52-0.86; P=0.002) and cardiovascular mortality (34.3% versus 52.3%; adjusted hazard ratio, 0.65; 95% confidence interval, 0.48-0.89; P=0.006) were significantly lower in women compared with men. With randomization to CABG+MED versus MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, cardiovascular mortality, or the composite of all-cause mortality or cardiovascular hospitalization (all P>0.05). In addition, surgical deaths were not statistically different (1.5% versus 5.1%; P=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG+MED versus MED on all-cause mortality, cardiovascular mortality, the composite of death or cardiovascular hospitalization, or surgical deaths in patients with ischemic left ventricular dysfunction. Thus, sex should not influence treatment decisions about CABG in these patients. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00023595.

Sex Difference in Patients with Ischemic Heart Failure Undergoing Surgical Revascularization: Results from the STICH Trial

BACKGROUND: Female sex is conventionally considered a risk factor for coronary artery bypass grafting (CABG) and has been included as a poor prognostic factor in multiple cardiac operative risk evaluation scores. We aimed to investigate the association of sex and the long-term benefit of CABG in patients with ischemic left ventricular (LV) dysfunction enrolled in the prospective Surgical Treatment for Ischemic Heart Failure Study (STICH) trial. METHODS: The STICH trial randomized 1212 patients [148 (12%) women and 1064 (88%) men] with CAD and LV ejection fraction (EF)≤ 35% to CABG + medical therapy (MED) versus MED alone. Long-term (10-year) outcomes with each treatment were compared according to sex. RESULTS: At baseline, women were older (63.4 vs 59.3, p=0.016) with higher BMI (27.9 vs 26.7, p=0.001). Women had more CAD risk factors (diabetes 55.4% vs 37.2%, hypertension 70.9% vs 58.6%, hyperlipidemia 70.3% vs 58.9%) except for smoking (13.5% vs 21.8%), and had lower rates of prior CABG (0% vs 3.4%, all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05) than men. Moreover, women had higher New York Heart Association (NYHA) class (Class III/IV 66.2% vs 57.0%), lower 6-min walk capacity (300m vs 350m) and lower Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary scores (51 vs 63) (all p<0.05). Over 10-years of follow up, all- cause mortality (49.0% vs 65.8%, adjusted HR 0.67, CI 0.52­0.86, p=0.002) and CV mortality (34.3% vs 52.3%, adjusted HR 0.65, CI 0.48­0.89, p=0.006) were significantly lower in women compared to men. With randomization to CABG + MED vs. MED treatment, there was no significant interaction between sex and treatment group in all-cause mortality, CV mortality, or the composite of all-cause mortality or CV hospitalization (all p>0.05). In addition, surgical deaths were not statistically different (1.5% vs 5.1%, p=0.187) between sexes among patients randomized to CABG per protocol as initial treatment. CONCLUSIONS: Sex is not associated with the effect of CABG + MED vs. MED on all-cause mortality, CV mortality, the composite of death or CV hospitalization, or surgical deaths in patients with ischemic LV dysfunction. Thus, sex should not influence treatment decisions regarding CABG in these patients.

Validation of the 2014 European Society of Cardiology Sudden Cardiac Death Risk Prediction Model in Hypertrophic Cardiomyopathy in a Reference Center in South America.

Sudden cardiac death (SCD) is a common cause of death in hypertrophic cardiomyopathy (HC). Our aim was to conduct an external and independent validation in South America of the 2014 European Society of Cardiology (ESC) SCD risk prediction model to identify patients requiring an implantable cardioverter defibrillator. This study included 502 consecutive patients with HC followed from March, 1993 to December, 2014. A combined end point of SCD or appropriate implantable cardioverter defibrillator therapy was assessed. For the quantitative estimation of individual 5-year SCD risk, we used the formula: 1 - 0.998(exp(Prognostic index)). Our database also included the abnormal blood pressure response to exercise as a risk marker. We analyzed the 3 categories of 5-year risk proposed by the ESC: low risk (LR) <4%; intermediate risk (IR) ≥4% to <6%, and high risk (HR) ≥6%. The LR group included 387 patients (77%); the IR group 39 (8%); and the HR group 76 (15%). Fourteen patients (3%) had SCD/appropriate implantable cardioverter defibrillator therapy (LR: 0%; IR: 2 of 39 [5%]; and HR: 12 of 76 [16%]). In a receiver-operating characteristic curve, the new model proved to be an excellent predictor because the area under the curve for the estimated risk is 0.925 (statistical C: 0.925; 95% CI 0.8884 to 0.9539, p <0.0001). In conclusion, the SCD risk prediction model in HC proposed by the 2014 ESC guidelines was validated in our population and represents an improvement compared with previous approaches. A larger multicenter, independent and external validation of the model with long-term follow-up would be advisable.

Trasplante cardiorenal combinado en la enfermedad cardíaca y renal avanzada / Combined cardiorenal transplant in heart and advanced renal disease

Introducción: la insuficiencia renal (IR) es predictor de morbimortalidad postrasplante cardíaco (TxC). El trasplante cardiorenal (TxCR) combinado en candidatos a TxC con enfermedad renal severa, es una opción terapéutica. Nuestro objetivo es evaluar los resultados y seguimiento del TxCR en un único Centro. Material y métodos: Entre febrero de 1993 y diciembre de 2014 se realizaron 442 TxC. Desde el año 2006 se efectuaron TxCR con único donante en 20 pacientes (p). Los criterios de selección fueron: IR con ClCr ≤ 40 mil/min o requerimiento de diálisis en candidatos a TxC. Todos los p recibieron timoglobulina e inmunosupresión con tacrolimus, micofenolato mofetil y esteroides. La mediana de seguimiento fue 46 meses (7-96). Resultados: Edad media 58±7 años y 85% eran hombres. La creatinina (Cr) media 3,1+-2,5 mg/ dl y ClCr 27,5+10 mil/min. Requirieron diálisis 3p en el período pre trasplante y 4p se encontraban en diálisis crónica. Etiología de miocardiopatías dilatadas: coronaria 10p, no coronaria 9p y reTxC 1p; nefropatías: nefroangioesclerosis 5p, síndrome cardiorenal 10p, diabetes 2p, glomerulopatía 1p, poliquistosis 1p y nefritis tóxica 1p. La Cr a 30 días y a 1 año del TxCR fue 1,2+-0,4 mm/dl y 1,1+-0,2 mg/dl respectivamente. La mortalidad hospitalaria fue de 3/20p (15%), 2p por sepsis y 1p por falla del injerto cardíaco. Mortalidad alejada 5/17p (29%), 4p por sepsis y 1p por sarcoma hepatocelular. La supervivencia a 1 y 3 años fue del 76 y 72%. Conclusiones: En nuestra serie el TxCR fue un tratamiento seguro y eficaz en candidatos a TxC y con ClCr < 40 mil/min.

Introduction: renal failure (RF) is a post cardiac transplantation predictor of morbimortality. The combined cardiorenal transplant (CCRTx) in cardiac transplantation (CTx) candidates with chronic renal disease is a therapeutic option. Our aim was to evaluate the CCRTx follow up outcomes in a single Centre. Methods: Between 2/1993 and 12/2014 we performed 442 CTx. Since 2006, 20 patients (p) underwent CCRTx using allografts from the same donor. The inclusion criteria were: RF with CrCl ≤ 40 mil/min or dialysis requirement in CTx candidates. All p received Thymoglobulin and immunosuppression with tacrolimus, mycophenolate mofetil and steroids.Median follow up: 46 months (7-96). Results: Mean age: 58±7 years, 85% were male. Mean Creatinine (Cr): 3,1+-2,5 mg/dl and ClCr 27,5+10 mil/min. Three p required dialysis during the pre-transplantation phase and 4 p were under chronic dialysis. Etiologies: cardiomyopathies: coronary 10 p, noncoronary 9 p and re CTx, 1 p; nephropathies: nephroangiosclerosis 5 p, cardiorenal syndrome 10 p, diabetes 2 p, glomerulopathy 1 p, polycystosis 1 p and toxic nephritis 1 p. At 30 days and 1 year post CCRTx, Cr was 1,2+-0,4 mg/dl and 1,1+-0,2 mg/dl respectively. In-hospital mortality was 3/20 p (15%), 2 p due to sepsis and 1 p due to cardiac graft failure. Late mortality 5/17 p (29 %), 4p due to sepsis and 1 p due to liver sarcoma. Survival at 1 and 3 years was 76 and 72%, respectively. Conclusions: In our series CCRTx was a safe and effective treatment for CTx candidates with CrCl < 40 ml/min.

Presence of antigen-experienced T cells with low grade of differentiation and proliferative potential in chronic Chagas disease myocarditis.

BACKGROUND: The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20-30% of infected individuals but not until 10-20 years after the initial infection. We have previously shown that circulating interferon-γ-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. METHODOLOGY/PRINCIPAL FINDINGS: The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3(+), CD4(+), CD8(+), CD45RO(+)) with a low grade of differentiation (CD27(+), CD57(-), CD45RA(-), PD(-)1(-)). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3(+) cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3(+) T cells, assessed by Ki67 staining, was found. CONCLUSIONS/SIGNIFICANCE: The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection.

Experiencia con bomba centrífuga magnética en pacientes con shock cardiogénico (INTERMACS 1) / Experience with Magnetically-Levitated Centrifugal Flow Pump in Patients with Cardiogenic Shock (INTERMACS 1)

Introducción El uso de dispositivos de asistencia ventricular a corto plazo con levitación magnética permite estabilizar hemodinámicamente a pacientes en shock cardiogénico refractario en estadio INTERMACS 1 y definir la estrategia terapéutica. Objetivos Evaluar los resultados, en un único centro, del uso de bomba centrífuga de segunda generación en pacientes con shock cardiogénico refractario. Material y métodos Se analizaron retrospectivamente 15 pacientes con asistencia ventricular con bomba Levitronix CentriMag® desde 2006 a 2011. Todos los pacientes presentaban shock cardiogénico refractario con dos inotrópicos y 13 tenían balón de contrapulsación intraaórtico previo a la asistencia. Las indicaciones fueron miocardiopatías avanzadas en 8 pacientes, miocarditis viral en 1, miocardiopatía periparto en 1, shock cardiogénico poscardiotomía en 3 y falla del injerto postrasplante cardíaco en 2 pacientes. Resultados La edad media en adultos fue de 49 ± 13 años y el 66% (10/15) eran hombres. Se implantó asistencia ventricular izquierda (AVI) en 1 paciente y asistencia biventricular (ABV) en 14. El tiempo medio de asistencia fue de 6 ± 4 días (2-19). La decisión terapéutica final posimplante fue puente al trasplante cardíaco en 12 pacientes (80%), puente a la recuperación en 1 (7%) y puente a la decisión en 2 (13%). La asistencia (ABV) se explantó en 1 paciente por recuperación de la función ventricular y 8 pacientes recibieron trasplante, con una supervivencia del 60% (9/15). Requirieron reoperación por sangrado 6 pacientes (40%) y 1 presentó trombosis de las cánulas; ningún paciente presentó accidente cerebrovascular ni fallas técnicas del sistema. Fallecieron bajo asistencia 6 pacientes (40%) (5 ABV y 1 AVI): 1 por sepsis, 1 con coagulopatía grave y 4 por falla multiorgánica. De los 6 pacientes fallecidos, 2 se encontraban con shock cardiogénico poscardiotomía y 4 eran candidatos previos a trasplante cardíaco. Conclusiones En esta serie, el soporte circulatorio con bomba centrífuga Levitronix CentriMag® fue efectivo en pacientes críticos, con una supervivencia del 60%. La complicación más frecuente fue la reoperación por sangrado.

Introduction Short term use of magnetically-levitated ventricular assist devices offers hemodynamic stabilization of patients with refractory cardiogenic shock in INTERMACS stage 1, enabling a therapeutic strategy. Objective The aira of this study was to assess in a single centre the results with second generation centrifugal flow pumps in patients with refractory cardiogenic shock. Methods Fifteen patients with Levitronix CentriMag® ventricular assist device implantation were retrospectively analyzed from 2006 to 2011. All patients presented refractory cardiogenic shock under two inotropic agents and 13 patients were also assisted with intra aortic balloon pump. The indications were: end stage cardiomyopathy in 8 patients, viral myocarditis in 1 patient, postpartum cardiomyopathy in 1 patient, post-cardiotomy cardiogenic shock in 3 patients and post heart transplantation graft failure in 2 patients. Results Mean age was 49 ± 13 years, and 66% (10/15) were men. Only 1 patient underwent left ventricular assist device implantation (LVA) and 14 patients underwent biventricular assistance (BVA). Mean support duration was 6 ± 4 days (2-19). Final post-implant therapeutic decisión was bridge to heart transplantation in 12 patients (80%), bridge to reoovery in 1 patient (7%) and bridge to decisión in 2 patients (13%). One patient was successfully weaned from BVA due to ventricular function recovery and 8 patients were transplanted, with a survival rate of 60% (9/15). Reoperation due to bleeding was performed in 6 patients (40%) and 1 patient presented cannulae thrombosis. None of the patients had stroke or technical system failures. Six patients died while receiving circulatory assistance (40%) (5 BVA and 1 LVA), 1 patient due to sepsis, 1 patient due to coagulopathy and 4 patients due to múltiple system organ failure. Out of the 6 deaths, 2 patients were in postcardiotomy cardiogenic shock and 4 were on heart transplantation waiting list. Conclusions In this series, circulatory support with Levitronix CentriMag® centrifugal flow pump was effective in critical patients with a survival rate of 60%. Reoperation for bleeding was the most frequent complication.