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.).

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.

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.

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.

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.

Myocardial viability and survival in ischemic left ventricular dysfunction.

BACKGROUND: The assessment of myocardial viability has been used to identify patients with coronary artery disease and left ventricular dysfunction in whom coronary-artery bypass grafting (CABG) will provide a survival benefit. However, the efficacy of this approach is uncertain. METHODS: In a substudy of patients with coronary artery disease and left ventricular dysfunction who were enrolled in a randomized trial of medical therapy with or without CABG, we used single-photon-emission computed tomography (SPECT), dobutamine echocardiography, or both to assess myocardial viability on the basis of prespecified thresholds. RESULTS: Among the 1212 patients enrolled in the randomized trial, 601 underwent assessment of myocardial viability. Of these patients, we randomly assigned 298 to receive medical therapy plus CABG and 303 to receive medical therapy alone. A total of 178 of 487 patients with viable myocardium (37%) and 58 of 114 patients without viable myocardium (51%) died (hazard ratio for death among patients with viable myocardium, 0.64; 95% confidence interval [CI], 0.48 to 0.86; P=0.003). However, after adjustment for other baseline variables, this association with mortality was not significant (P=0.21). There was no significant interaction between viability status and treatment assignment with respect to mortality (P=0.53). CONCLUSIONS: The presence of viable myocardium was associated with a greater likelihood of survival in patients with coronary artery disease and left ventricular dysfunction, but this relationship was not significant after adjustment for other baseline variables. The assessment of myocardial viability did not identify patients with a differential survival benefit from CABG, as compared with medical therapy alone. (Funded by the National Heart, Lung, and Blood Institute; STICH ClinicalTrials.gov number, NCT00023595.).

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.

Terapia de resincronización cardíaca. Evolución a largo plazo de los pacientes respondedores y no respondedores / Cardiac Resynchronization Therapy. Long-term Evolution of Responder and Non-responder Patients

RESUMEN Introducción: La terapia de resincronización cardíaca (TRC) es un tratamiento eficaz en pacientes con insuficiencia cardíaca (IC), baja fracción de eyección del ventrículo izquierdo (FEVI) y QRS ancho. Sin embargo, hay un porcentaje de estos que son no respondedores, lo que implicaría peores resultados clínicos. Objetivos: Valorar las diferencias en parámetros ecocardiográficos de remodelado reverso y tasa de eventos [hospitalización por insuficiencia cardíaca (HIC), muerte de todas las causas (MT), trasplante cardíaco (TXC) y terapias apropiadas (TA)] entre pacientes respondedores vs. no respondedores a la TRC. Material y métodos: Se incluyeron 343 pacientes con TRC. Se los clasifico en respondedores y no respondedores según parámetros clínicos y ecocardiográficos. Se realizó seguimiento a 2 años, en que se evaluó el remodelado reverso y la incidencia de HIC, MT, TXC y TA. Resultados: De los 343 pacientes, 17% fueron no respondedores y 83% respondedores. A los 6 meses y 12 meses no hubo diferencias significativas en cuando a diámetros ventriculares, pero si en la FEVI (p<0,001), que aumentó más en los respondedores. A los 24 meses los respondedores presentaron menor diámetro diastólico (p=0,004), menor diámetro sistólico (p=0,003) y mayor FEVI (p<0,001) Los no respondedores tuvieron significativamente mayor incidencia de HIC (p< 0,001), TXC (p=0,001) y TA (p=0,002) y un exceso de MT en el límite de la significación estadística (p= 0,056). Conclusiones: Los pacientes respondedores a la TRC presentaron mayor remodelado reverso y mejor evolución clínica, en forma acorde a los resultados de estudios observacionales internacionales.

ABSTRACT Background: Cardiac resynchronization therapy (CRT) is an effective treatment in patients with heart failure (HF), low left ventricular ejection fraction (LVEF) and wide QRS. However, there are a percentage of these patients who are non-responders, implying worse clinical outcomes. Objectives: The aim of this study was to assess the differences in echocardiographic parameters of reverse remodeling and event rates [hospitalization for heart failure (HHF), all-cause mortality (ACM), heart transplantation (HTX) and appropriate therapies (AT)] between responder vs. non-responder patients to CRT. Methods: A total of 343 patients with CRT, classified into responders and non-responders according to clinical and echocardiographic parameters, were included in the study. A 2-year follow-up was performed, in which reverse remodeling and the incidence of HHF, ACM, HTX and AT were evaluated. Results: Among the 343 patients, 17% were non-responders and 83% responders. At 6 and 12 months there were no significant differences in ventricular diameters, but significant differences in LVEF (p<0.001), with greater increase in responders. At 24 months, responders had smaller diastolic diameter (p=0.004), smaller systolic diameter (p=0.003) and higher LVEF (p<0.001). Non-responders had significantly higher incidence of HHF (p<0.001), HTX (p=0.001) and AT (p=0.002), and an excess of ACM at the limit of statistical significance (p= 0.056). Conclusions: Patients responding to CRT presented greater reverse remodeling and better clinical evolution, in accordance with the results of international observational studies.

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.

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.

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.

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.

Comparison of prevalence, clinical course, and pathological findings of left ventricular systolic impairment versus normal systolic function in patients with hypertrophic cardiomyopathy.

Impaired left ventricular systolic function (ILVSF) in hypertrophic cardiomyopathy (HC) is a risk factor for sudden death and a determinant of high mortality. We determined its prevalence, clinical parameters, long-term outcome, and pathologic findings of explanted hearts. We retrospectively analyzed 382 patients with HC; ILVSF was characterized by LV ejection fraction <50% at rest and was identified in 24 patients (6.3%). Patients with ILVSF were younger than patients with normal SF (43.5 ± 14.1 vs 55.3 ± 20.4 years, p = 0.001) and had larger LV end-diastolic cavity diameter (53.2 ± 12.2 vs 43.8 ± 6.2 mm, p = 0.001), larger left atrium (51.2 ± 6.5 vs 44.3 ± 8 mm, p <0.001), and lower fractional shortening (30.7 ± 11.1% vs 45.5% ± 10.3%, p <0.001). A combined end point (heart failure death or heart transplantation) was considered. Median follow-up was 3 years (1.2 to 6.3). Fourteen patients with ILVSF (58.3%) had the end point compared to 3 (0.8%) with normal SF (p <0.001). In explanted hearts, fibrosis represented 30.5 ± 12.5% of the left ventricle; we observed a direct correlation between fibrosis and ventricular dilation (r = 0.794, p = 0.001) and an inverse correlation between fibrosis and ejection fraction (r = -0.623, p = 0.023). Number and length density of small arterioles (<50 µm in diameter) were significantly decreased. In conclusion, ILVSF in HC has a poor prognosis and is associated with fibrosis and selective decreased development of small arterioles.

Cardiomyocyte hypertrophy, oncosis, and autophagic vacuolization predict mortality in idiopathic dilated cardiomyopathy with advanced heart failure.

OBJECTIVES: The aim of this study was to identify the remodeling parameters cardiomyocyte (CM) damage or death, hypertrophy, and fibrosis that may be linked to outcomes in patients with advanced heart failure (HF) in an effort to understand the pathogenic mechanisms of HF that may support newer therapeutic modalities. BACKGROUND: There are controversial results on the influence of fibrosis, CM hypertrophy, and apoptosis on outcomes in patients with HF; other modalities of cell damage have been poorly investigated. METHODS: In endomyocardial biopsy specimens from 100 patients with idiopathic dilated cardiomyopathy and advanced HF, CM diameter and the extent of fibrosis were determined by morphometry. The proportion of CMs with evidence of apoptosis, autophagic vacuolization (AuV), and oncosis was investigated by immunohistochemical methods and by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling. Those parameters were correlated with mortality in 3 years of follow-up by univariate analysis and with multivariate models incorporating the clinical variables more relevant to the prediction of outcomes. RESULTS: CM AuV occurred in 28 patients (0.013 ± 0.012%) and oncosis in 41 (0.109 ± 0.139%). Nineteen patients showed both markers. Apoptotic CM nuclei were observed in 3 patients. In univariate analysis, CM diameter and AuV, either alone or associated with oncosis, were predictors of mortality. In multivariate analysis, CM diameter (hazard ratio: 1.37; 95% confidence interval: 1.12 to 1.68; p = 0.002) and simultaneous presence in the same endomyocardial biopsy specimen of AuV and oncosis (hazard ratio: 2.82; 95% confidence interval: 1.12 to 7.13; p = 0.028) were independent predictors of mortality. CONCLUSIONS: CM hypertrophy and AuV, especially in association with oncosis, are predictors of outcome in patients with idiopathic dilated cardiomyopathy and severe HF.

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.

Hipertensión arterial pulmonar: Registro de un centro de referencia en Argentina / Pulmonary Arterial Hypertension. A Registry at a Reference Centre in Argentina Introduction and objectives

Introducción y objetivos: En Argentina, no se conocen datos de pacientes con hipertensión pulmonar (HP) con diagnóstico de certeza. El propósito del presente registro fue conocer las características de nuestra población de pacientes con HP del Grupo I de la clasificación de Dana Point 2008, hipertensión arterial pulmonar (HAP), estudiar la supervivencia y las variables asociadas a mayor mortalidad. Métodos: Estudio de cohorte de 134 pacientes admitidos por primera vez en el consultorio de HP de nuestra institución en el período comprendido entre enero/2004 y marzo/2012. Se excluyeron 9 pacientes; total analizado: 125 pacientes. Resultados: Edad promedio: 34 ± 15,7 años y la relación mujer/hombre: 3,8/1. Las etiologías más prevalentes fueron la HAP idiopática (HAPI) (61, 48.8%), asociadas a cardiopatías congénitas (35, 28%) y a colagenopatías (18, 14.4%). La supervivencia libre de trasplante o muerte fue de 63.2%; a 12, 24 y 36 meses la supervivencia fue del 94% (IC95% 88-97), 90% (IC95% 83-94) y 83% (IC95% 75-89), respectivamente. Las variables basales asociadas a mayor mortalidad y/o trasplante fueron la disnea clase funcional III/IV (OR 3.6 IC95% 1.5-8.9, p < 0.01), la distancia recorrida en la prueba de la caminata de 6 minutos menor de 380 m (OR 2.7 IC95% 1.1-6.5 p = 0.023) y el derrame pericárdico (OR 4.2 IC95% 1.3-14.6 p = 0.021). Conclusiones: Esta serie muestra las características y supervivencia actuales de pacientes con HP en un centro de referencia en Argentina. Variables de fácil obtención y reproducción permitieron estratificar subgrupos de mayor riesgo de muerte y/o trasplante en el seguimiento.

Introduction and objectives: There are no data on outcome of patients with pulmonary hypertension (PH) in Argentina. The objective of this registry was to assess the characteristics of patients with PH belonging to the Group I Dana Point's 2008 classification, pulmonary arterial hypertension (PAH), and to identify variables associated with outcomes. Methods: One hundred and thirty four patients were analyzed in a consecutive sequence. After excluding nine patients, 125 patients were analyzed. Results: The patients mean age was 34 years (SD±15,7) and the female/male ratio was 3.8/1. The most prevalent aetiologies were: idiopathic PAH (IHAP) (61, 48.8%), PH associated to congenital heart disease (35, 28%) and PH associated to connective tissue disease (18, 14.4%). Overall survival, excluding transplantation, was 63.2%; at 12, 24 and 36 months survival was 94% (CI 95% 88-97), 90% (CI 95% 83-94) and 83% (CI 75-89), respectively. Baseline variables associated to increased mortality or need for transplantation were functional class III/IV (NYHA) (OR 3.6 CI 95% 1.5-8.9, p <0.01), 6 minute-walk test distance shorter than 380 m (OR 2.7 CI 95% 1.1-6.5 p = 0.023) and pericardial effusion (OR 4.2 CI 95% 1.3-14.6 p = 0.021). Conclusion: This series shows characteristics and survival of patients with pulmonary arterial hypertension at a reference centre in Argentina. Some readily available variables allowed us to stratify subgroups at a higher risk of death and/or transplantation during the follow up.

Predictores de Mortalidad o trasplante cardíaco en la miocardiopatía periparto / Predictors of Mortality or Heart Transplantation in Peripartum Cardiomyopathy

Introducción La miocardiopatía periparto es una forma infrecuente de insuficiencia cardíaca congestiva con una evolución impredecible. Su verdadera incidencia y prevalencia no se conoce con certeza y su etiología aún no se ha aclarado, aunque se han involucrado varios mecanismos en los que se reconocen diversos factores de riesgo. Objetivo Analizar predictores pronósticos de mortalidad o de requerimiento de trasplante cardíaco. Material y métodos Entre 1992 y noviembre de 2011 se evaluaron retrospectivamente 23 pacientes. En aquellas con insuficiencia cardíaca descompensada se realizó monitorización hemodinámica. La mediana de seguimiento fue de 7,3 años (3,2-17,5). El análisis univariado se realizó por regresión de Cox y la supervivencia global se calculó con el método de Kaplan-Meier. Resultados La edad media fue de 28,7 ± 8,8 años, ocho pacientes eran multíparas. El 73% estaban en clase funcional III-IV. La presión arterial sistólica y diastólica fue de 103 ± 23 y 67 ± 11 mm Hg, respectivamente, y la frecuencia cardíaca, de 92 ± 19 lpm. El 100% se encontraba en ritmo sinusal. El índice cardiotorácico fue de 0,56 ± 0,07. El diámetro diastólico y sistólico del ventrículo izquierdo fue de 67,5 ± 10,2 y 56,7 ± 10,1 mm, respectivamente, el diámetro auricular izquierdo fue de 42,5 ± 6 mm y la fracción de eyección del ventrículo izquierdo, del 24,6% ± 10,8%. La presión media de la arteria pulmonar fue de 25 ± 9 mm Hg y la capilar pulmonar, de 18,4 ± 7,8 mm Hg; el índice cardíaco fue de 2,6 ± 0,6 L/min/m². Siete pacientes fallecieron y tres fueron sometidas a trasplante cardíaco. En el análisis univariado, la clase funcional, el índice cardíaco, la presión arterial sistólica y diastólica, la presión capilar y pulmonar media, el índice cardiotorácico y el diámetro auricular izquierdo se asociaron con mortalidad y trasplante cardíaco. La supervivencia a 1, 3 y 6 años fue del 91%, 82% y 64%, respectivamente. Conclusiones La mortalidad hospitalaria fue del 4,3% y el requerimiento de trasplante cardíaco o la muerte en el seguimiento fueron del 39%. Los parámetros hemodinámicos al ingreso fueron los principales predictores de mortalidad y de trasplante.

Background Peripartum cardiomyopathy is an uncommon form of congestive heart failure with an unpredictable outcome. Very little is known about its real incidence and prevalence, and its etiology is still unknown, although a number of contributing factors, including diverse risk factors, have been proposed. Objective To analyze the predictors of mortality or need for heart transplantation. Methods Between 1992 and November 2011, 23 patients were retrospectively evaluated. Patients with decompensated heart failure were managed with hemodynamic monitoring. Me­dian follow-up was of 7.3 years (3.2-17.5). Univariate Cox regression analysis was performed and overall survival was calculated using the Kaplan-Meier method. Results Mean age was 28.7±8.8 years; eight patients were multipara. Seventy three percent were in functional class III-IV. Systolic blood pressure and diastolic blood pressure were 103±23 and 67±11 mm Hg, respectively, and heart rate was 92±19 bpm. All the patients were in sinus rhythm. The cardiothoracic index was 0.56±0.07. End-diastolic and end-systolic left ventricular dimensions were 67.5±10.2 and 56.7±10.1 mm, respectively; left atrial dimension was 42.5±6 mm and left ventricular ejection fraction was 24.6%±10.8%. Mean pulmonary artery pressure was 25±9 mm Hg and pulmonary wedge pressure, was 18.4±7.8 mm Hg; cardiac index was 2.6±0.6 L/min/m². Seven patients died and three patients underwent heart transplantation. Univariate analysis revealed that functional class, cardiac index, systolic and diastolic blood pressure, pulmonary wedge pressure and mean pulmonary artery pressure, cardiothoracic index and left atrial dimension were associated with mortality and heart transplantation. Survival at one, three and six years was of 91%, 82% y 64%, respectively. Conclusions In-hospital mortality was of 4.3% and the need for heart transplantation or mortality during follow-up was of 39%. The hemodynamic parameters at admission were the main predictors of mortality and transplant.

Hipertensión pulmonar grave reversible asociada al uso de dasatinib en un paciente con leucemia mieloide crónica / Reversible Severe Pulmonary Arterial Hypertension Associated to Dasatinib in a Chronic Myeloid Leukaemia Patient

La hipertensión arterial pulmonar (HAP) es una enfermedad rara caracterizada por un incremento progresivo de las resistencias vasculares pulmonares que lleva a la falla cardíaca derecha y muerte prematura. La enfermedad puede ser idiopática o asociada a otras condiciones como la hipertensión portal, el virus de la inmunodeficiencia humana, las enfermedades del tejido conectivo, las cardiopatías congénitas con cortocircuitos de izquierda a derecha o asociadas a diferentes toxinas o drogas. Se han realizado avances en el tratamiento farmacológico enfocados en el remodelado de la vasculatura pulmonar. En este sentido, se encuentran en evaluación los inhibidores de la tirosina kinasa (ITK). El imatinib es un ITK selectivo aprobado para el tratamiento de la leucemia mieloide crónica (LMC) que ha demostrado beneficios en el tratamiento de la HAP en estudios de fase II. Paradójicamente, el ITK dasatinib, también aprobado para el tratamiento de la LMC, ha sido asociado a HAP, falla ventricular derecha y a derrame pleural, lo que sugiere la posibilidad de un efecto adverso a nivel pulmonar vinculado con esta droga.

Pulmonary arterial hypertension is a rare disease that is characterized by a progressive increase in vascular pulmonary resistance, chronic right ventricle failure and premature death. Pulmonary arterial hypertension can be either idiopathic or associated to other conditions such as portal hypertension, human immunodeficiency virus, connective tissue diseases, congenital systemic-to-pulmonary shunts or associated to different drugs/toxins. Encouraging progress has been made by targeting the main vasoproliferative aspects of the disease. Tyrosine kinase inhibitors (TKI) are promising emerging therapeutics. Imatinib, a selective TKI approved for the treatment of chronic myeloid leukaemia, has demonstrated some efficacy in treating pulmonary arterial hypertension in a phase II study. However, the TKI dasatinib, also approved for therapy of chronic myeloid leukaemia, has been linked to reversible pulmonary arterial hypertension and right ventricular failure, with pleural effusion, suggesting the possibility of drug-related pulmonary arterial hypertension.

Miocardiopatía no compactada: Estratificación de riesgo de muerte súbita para indicación de cardiodesfibrilador automático implantable / Non-Compaction Cardiomyopathy: Risk Stratification of Sudden Death for Automatic Cardioverter Defibrillator Implantation

Introducción La miocardiopatía no compactada es una entidad rara. Su historia natural incluye insuficiencia cardíaca, eventos tromboembólicos, arritmias y muerte súbita (MS). En ausencia de datos de estudios aleatorizados o registros, las Guías ACC/AHA/HRS 2008 recomiendan el cardiodesfibrilador automático implantable (CDAI) en todos los pacientes con miocardiopatía no compactada para reducir el riesgo de muerte súbita. Objetivo Describir la evolución de pacientes con miocardiopatía no compactada de acuerdo con criterios seleccionados de estratificación de riesgo de muerte súbita para decidir el implante de un CDAI. Material y métodos Se analizaron 80 pacientes. El diagnóstico se estableció mediante criterios ecocardiográficos y de resonancia magnética nuclear cardíaca. Los criterios para el implante de un CDAI como prevención secundaria incluyeron muerte súbita y taquicardia ventricular sostenida (TVS); como prevención primaria comprendieron fracción de eyección del ventrículo izquierdo (FEVI) < 30% o ≥ 2 factores de riesgo (antecedentes familiares de muerte súbita [AFMS], síncope y TV no sostenida). Resultados Grupo CDAI (n = 26) para prevención secundaria (n = 3): 3 pacientes sufrieron muerte súbita (2 TVS). Grupo CDAI para prevención primaria (n = 23): 10 pacientes tuvieron FEVI < 30%, 1 FEVI < 30% + AFMS, 1 FEVI < 30% + síncope, 5 FEVI < 30% + TV no sostenida, 3 TV no sostenida + síncope, 2 TV no sostenida + AFMS y 1 TVS en estudio electrofisiológico. El seguimiento fue de una mediana de 16,61 meses. Dos pacientes fueron sometidos a un trasplante cardíaco, 3 recibieron choques apropiados y 4 pacientes, choques inapropiados. Grupo sin CDAI (n = 54): 4 pacientes tuvieron síncope y 4 TV no sostenida. El seguimiento fue de una mediana de 12,15 meses. Dos pacientes fallecieron por insuficiencia cardíaca y 3 fueron sometidos a un trasplante cardíaco. Conclusiones El 32,5% de los pacientes con miocardiopatía no compactada recibieron un CDAI, el 88,5% por prevención primaria; el 11,5% recibieron choques apropiados. No hubo muerte súbita en pacientes sin CDAI; la muerte sobrevino por progresión de la insuficiencia cardíaca. Este registro sugiere que los pacientes con miocardiopatía no compactada podrían estratificarse para seleccionar a aquellos que tienen mayor riesgo de muerte súbita y podrían beneficiarse con el implante de un CDAI.

Background Non-compaction cardiomyopathy is a rare disease. The natural history of this condition includes heart failure, thromboembolic events, arrhythmias and sudden death (SD). In the absence of information from randomized studies or registries, the 2008 ACC/AHA/HRS guidelines recommended cardioverter defibrillator implantation in all patients with non-compaction cardiomyopathy to reduce the risk of sudden death. Objective To describe the outcomes of patients with non-compaction cardiomyopathy according to the selection criteria used for risk stratification of sudden death for automatic implantable cardioverter defibrillator therapy. Material and Methods A total of 80 patients were analyzed. The diagnosis was made using criteria from echocardiography and cardiac magnetic resonance imaging. The criteria used for implantation of an ICD were sudden death and sustained ventricular tachycardia (SVT) for secondary prevention, and left ventricular ejection fraction (LVEF) <30% or ≥2 risk factors (family history of sudden death [FHSD], syncope and non-sustained VT). Results Group ICD (n=26) for secondary prevention (n=3): 3 patients presented sudden death (2 SVT). Group ICD for primary prevention (n=23): 10 patients had LVEF <30%, 1 LVEF <30% + FHSD, 1 LVEF <30% + syncope, 5 LVEF <30% + nonsustained VT, 3 non-sustained VT + syncope, 2 non-sustained + FMSD and 1 VT in the electrophysiologic study. Median follow-up was 16.61 months. Two patients underwent heart transplantation, 3 received appropriate ICD shocks, while ICD shocks were inappropriate in 4 patients. Group without ICD (n=54): 4 patients presented syncope and 4 non-sustained VT. Median follow-up was 12.15 months. Two patients died due to heart failure and 3 underwent cardiac transplantation. Conclusions ICD was implanted in 32.5% of patients with non-compaction cardiomyopathy, 88.5% for primary prevention; appropriate shocks were received in 11.5% of patients. None of the patients who did not receive an ICD presented sudden death; these patients died due to heart failure progression. This registry suggests that patients with non-compaction cardiomyopathy might be stratified to select those at a higher risk of sudden death who might beneficiate from ICD therapy.