Disfunção Ventricular e do Átrio Esquerdo Subclínica em Pacientes com Acromegalia: Um Estudo de Ecocardiograma de Rastreamento de Manchas / Subclinical Left Atrial and Ventricular Dysfunction in Acromegaly Patients: A Speckle Tracking Echocardiography Study

Resumo Fundamento Embora se saiba que a fração de ejeção (FE) do ventrículo esquerdo (VE) medida por eletrocardiograma seja preservada em pacientes com acromegalia, não há informação suficiente sobre deformação longitudinal global e deformação do átrio esquerdo (SLG-VE e SAE). Objetivo O objetivo deste estudo foi avaliar as funções do ventrículo esquerdo (VE) e do átrio esquerdo (AE) por ecocardiograma strain (ES) em pacientes com acromegalia. Métodos Este estudo incluiu 50 pacientes com acromegalia na forma ativa da doença e 50 controles saudáveis com idade, sexo e área de superfície corporal similares. Além dos ecocardiogramas de rotina, medições de SLG-VE e SAE foram realizadas com o ES. Resultados Os valores dos SAE e SLG-VE foram significativamente mais baixos em pacientes com acromegalia (p<0,05 para todos). Na análise bivariada, a pressão arterial sistólica, o pró-hormônio N-terminal do peptídeo natriurético cerebral, o fator de crescimento semelhante à insulina tipo 1, e detectou-se que os níveis de IMVE tinham correlação positiva com SAE e SLG-VE (p<0,05). O nível de IGF-1 tinha forte correlação com SAE e SLG-VE (p<0,001 e β=0,5 vs. p<0,001 e β=0,626, respectivamente); 48% dos pacientes com acromegalia têm SLG-VE reduzido (<20%). O índice de massa do ventrículo esquerdo (IMVE) determina independentemente a presença de SLG-VE reduzido, e cada 1g/m2 de aumento no nível de IMVE aumenta a probabilidade de redução de SLG-VE em 6%. Conclusão Embora a fração de ejeção de VE seja normal em pacientes com acromegalia, os valores de SAE e SLG-VE são significativamente mais baixos. Além do aumento em IMVE, outro achado do envolvimento cardíaco pode ser a redução de SAE e SLG-VE. Portanto, além do ecocardiograma de rotina, SAE e SLG-VE podem ser úteis para avaliar os sinais iniciais de envolvimento cardíaco antes da ocorrência de alterações cardíacas irreversíveis.

Abstract Background Although it is known that the left ventricular (LV) ejection fraction (EF) measured by echocardiography is preserved in patients with acromegaly, there is not enough information about the LV and left atrial strain (LV-GLS and LAS). Objective This study aimed to evaluate the left ventricular (LV) and left atrial (LA) functions with strain echocardiography (SE) in patients with acromegaly. Methods This study included 50 acromegaly patients with active disease and 50 healthy controls with similar age, gender, and body surface area. In addition to routine echocardiography examinations, LV-GLS and LAS measurements were performed with SE. Results LAS and LV-GLS values were significantly lower in patients with acromegaly (p<0.05 for all). In bivariate analysis, systolic blood pressure, N-terminal prohormone of brain natriuretic peptide, Insulin-like growth factor-1, LA diastolic diameter, and LVMI levels were found to be positively correlated with both LAS and LV-GLS (p <0.05). IGF-1 level was strongly correlated with LAS and LV-GLS (p<0.001 and β=0.5 vs. p<0.001 and β=0.626, respectively); 48% of patients with acromegaly have reduced LV-GLS (<20%). Left ventricular mass-index (LVMI) independently determines the presence of reduced LV-GLS and each 1g/m2increase in LVMI level increases the likelihood of reduced LV-GLS by 6%. Conclusion Although LV ejection fraction is normal in patients with acromegaly, LAS and LV-GLS values were significantly reduced. Apart from LVMI increase, another finding of cardiac involvement may be LAS and LV-GLS decrease. Therefore, in addition to routine echocardiography, LAS and LV-GLS may be useful to evaluate early signs of cardiac involvement before the occurrence of irreversible cardiac changes.

Deslocamento linear longitudinal do ventrículo esquerdo comparado ao strain longitudinal global por ressonância magnética cardiovascular / Left ventricular longitudinal linear displacement versus global longitudinal strain on cardiovascular magnetic resonance

Introdução: A função sistodiastólica do ventrículo esquerdo é prognóstica nas doenças cardiovasculares e pode ser avaliada por strain longitudinal global por meio de ecocardiografia e de ressonância magnética cardíaca. O strain longitudinal global pela ressonância magnética cardíaca exige a utilização de software de alto custo. O deslocamento linear longitudinal do ventrículo esquerdo pode ser uma alternativa simples e barata ao strain longitudinal global, porém eles não foram ainda comparados sistematicamente. Objetivo: Comparar o deslocamento linear longitudinal com o strain longitudinal global e fração de ejeção do ventrículo esquerdo em valvopatas aórticos e controles. Métodos: Incluímos 44 participantes (26 valvopatas aórticos/19 controles). O strain longitudinal global utilizou software específico (Circle Cardiovascular Imaging 42) e o deslocamento linear longitudinal apenas medidas lineares de distância entre a base e o ápex do ventrículo esquerdo, gerando deslocamento máximo, velocidade máxima no início da diástole, velocidade na diástase e a relação entre velocidade na diástase e velocidade máxima no início da diástole. Resultados: Deslocamento máximo e velocidade máxima no início da diástole correlacionaram-se com strain longitudinal global (r=0,69 e r=0,65 respectivamente) e com a fração de ejeção do ventrículo esquerdo (r=0,47 e r=0,57, p<0,001 para ambos). Deslocamento máximo e velocidade máxima no início da diástole apresentaram área sob a curva Característica de Operação do Receptor de 0,88 e 0,91 e, no melhor ponto de corte (-0,13 e 0,66), sensibilidade de 72,43% e 57,14% e especificidade 80,65% e 87,10%, respectivamente, quando comparados ao strain longitudinal global. Utilizando a fração de ejeção do ventrículo esquerdo como referência, foram obtidos 0,70 e 0,82, e, no melhor ponto de corte (-0,11 e 0,61), sensibilidade de 75,00% e 50,00% e especificidade 72,97% e 78,38%, respectivamente. Conclusão: O deslocamento linear longitudinal foi semelhante ao strain longitudinal global. O deslocamento máximo derivado do deslocamento linear longitudinal foi o melhor parâmetro na sístole, enquanto a velocidade máxima no início da diástole foi o melhor na diástole, o que possibilita a avaliação da função diastólica pela ressonância magnética cardíaca na rotina clínica de forma rápida e sem custo adicional.(AU)

Background: Left ventricular (LV) systolic diastolic function is prognostic in cardiovascular diseases and can be assessed via global longitudinal strain (GLS) on echocardiography and cardiac magnetic resonance (CMR). However, GLS by CMR requires the use of expensive software. Longitudinal linear displacement (LLD) may be a simple and inexpensive alternative to GLS, but the two have not been systematically compared. Objective: To compare LLD with GLS and LV ejection fraction (LVEF) in aortic valve disease patients and controls. Methods: We included 44 participants (26 with aortic valve disease, 19 controls). GLS was determined using CVI42 software (Circle Cardiovascular Imaging), while the LLD linear measurements of the distance between the base/apex of the LV included maximum displacement (MD), maximum velocity in early diastole (MVED), atrioventricular junction velocity in diastasis (VDS), and VDS/MVED ratio. Results: DM and MVED were correlated with GLS (r=0.69 and r=0.65, respectively) and LVEF (r=0.47 and r=0.57, p<0.001 for both). DM and MVED showed areas under the receiver operating characteristic curve (AUC) of 0.88 and 0.91, and at the best cut-off point (-0.13 and 0.66), sensitivities of 72.43% and 57.14% and specificities of 80.65% and 87.10%, respectively, compared to GLS. Using LVEF as a reference, we obtained AUC of 0.70 and 0.82, and at the best cut-off point (-0.11 and 0.61), sensitivities of 75.00% and 50.00% and specificities of 72.97% and 78.38%, respectively. Conclusion: LLD demonstrated similar performance to that of GLS. MD derived from LLD was the best parameter during systole, while MVED was the best during diastole. Our findings demonstrate the routine, quick, and inexpensive assessment of diastolic function on CMR.(AU)

Clinical features of Chinese patients with Takotsubo syndrome / 中华心血管病杂志

Objective: To analyze the characteristics, diagnosis and treatment status of Takotsubo syndrome (TTS) of Chinese patients. Methods: Complete literature review was performed to summarize Chinese TTS cases between 2007 and 2018. Results: A total of 131 literatures were included including 160 TTS patients (age (58.3±14.7) years). There were 137 female patients (85.6%) in this cohort, the age was (59.6±14.0) years. There were 124 cases (77.5%) of stress-evoking factors, of which 83 cases (66.9%) were self-stress factors. There were 97 cases (60.6%) complained of chest pain and 15 cases (9.4%) with syncope. Forty-eight cases (30.0%) presented with cardiogenic shock. CK-MB and cTnT/I increased in 109 cases (80.1%). There were 124 cases (77.5%) presented with ST segment elevation on electrocardiogram, which were common in lead V2-V5. Echocardiography results were available in 128 cases (80.0%), reduced left ventricular ejection fraction (<50%) was reported in 78 cases (73.6%). Coronary angiography was performed in 133 patients (83.1%), of which 126 patients (94.7%) had normal coronary arteries or single non-significant stenosis. One hundred and thirty-eight patients (87.3%) were apical type. The misdiagnosis rate on admission was 96.9% (155/160), of which 141 cases (88.1%) were misdiagnosed as acute myocardial infarction. Nitroglycerin was used in 36 patients (30.3%). Angiotensin converting enzyme inhibitor or angiotensin Ⅱ receptor antagonist were used in 38 patients (31.9%). β blockers were used in 46 patients (38.7 %). Dopamine was used in 22 cases (18.5%) and norepinephrine was used in 12 cases (10.1%). Intra-aortic balloon counter pulsation was used in 5 cases (3.1%). Cardiopulmonary resuscitation was performed in 9 cases (5.6%). Cardiac function recovery time was 7 (6, 15) days. The average InterTAK diagnosis score was (51.5±18.1) points, and value was>70 points in 2 cases (1.3%). There were 92 patients in the high-risk group, and there were 3 recurrent TTS cases. Five patients died. Conclusions: TTS incidence tends to be young and dominates in female in China. The misdiagnosis rate is extremely high on admission. Most patients are treated with medication.

Impact of empagliflozin on peak oxygen uptake in HFmrEF patients: a randomized controlled trial / 中华心血管病杂志

Objective: To evaluate the impact of empagliflozin on peak oxygen uptake (VO2peak) in patients with heart failure with mildly reduced ejection fraction (HFmrEF). Methods: In this randomized controlled trial, consecutive HFmrEF patients admitted to the Department of Cardiology of China-Japan Friendship Hospital from September 2019 to October 2020 were screened, and randomly assigned to empagliflozin group (EG) or conventional group (CG) using a random number table. The enrolled patients were treated according to the guidelines, and patients in the empagliflozin group received additional empagliflozin (10 mg, once a day, orally) on top of the conventional treatment. The primary end points were VO2peak at 6 months after treatment, and the secondary end points included other parameters of cardiopulmonary exercise test (CPET), 6-minute walking distance, N-terminal B-type pro-natriuretic peptide (NT-proBNP) level, and Kansas City Cardiomyopathy Questionnaire (KCCQ) score. Results: A total of 112 patients were included (mean age 69 (57, 78) years, 84 male (75.0%)). There were 55 cases in CG group and 57 cases in EG group. There were no significant differences in baseline data including age, sex, body mass index, left ventricular ejection fraction, systolic blood pressure, heart rate, estimated glomerular filtration rate, glycosylated hemoglobin, hemoglobin, NT-proBNP, daily dose of tolasemi, combined medication, CPET parameters, the proportion of New York Heart Association heart function Ⅲ/Ⅳ, history of coronary heart disease, history of hypertension, history of diabetes (all P>0.05). At 6 months after treatment, VO2peak was significantly higher in EG group than in CG group(P=0.023). VE/VCO2 slope was significantly lower in EG group than in CG group(P=0.034). Oxygen uptake efficiency slope was significantly higher in EG group than in CG group(P=0.038). The level of NT-proBNP was significantly lower in EG group than in CG group(P=0.020). Six-minute walking distance was significantly higher in EG group than in CG group(P=0.037). KCCQ score was significantly higher in EG group than in CG group(P=0.048). Exercise oscillatory ventilation decreased in both groups (1 case in each group, P>0.05). Conclusion: Empagliflozin can significantly improve VO2peak in patients with HFmrEF.

Prevalencia de disfunción diastólica de acuerdo con las guías diagnósticas de 2009 y 2016. Relación con la valoración hemodinámica no invasiva / Prevalence of diastolic dysfunction (DD) according to the diagnostic guidelines of 2009 and 2016. Relationship with non-invasive hemodynamic assessment

Resumen Objetivos: Evaluar la prevalencia de DD de acuerdo con los criterios de las guías del 2009 y 2016, y su relación con la distensibilidad arterial sistémica (DAS) y la resistencia vascular periférica (RVP). Material y métodos: Se analizó a 306 pacientes ≥ 40 años de edad, con fracción de expulsión ≥ 50%. Se calcularon en todos DAS y RVP. Resultados: La prevalencia de DD fue de 32.7% y 22.9% según las guías de 2009 y 2016, respectivamente (p = < 0.0001). De acuerdo con las guías del 2009, los pacientes con DD presentaron una media de DAS menor que aquéllos con función normal (p = 0.0001), de modo similar a las guías del 2016 (p = 0.0007). La DD, según las guías de 2009 y 2016, mostró valores más altos de RVP que los normales (p = 0.005 y p = 0.018, respectivamente). Asimismo, la DD fue predictora, en el análisis univariado, de DAS < 0.60 ml.mm Hg-1 y RVP > 1,400 mmHg.min.l-1 según ambas guías. En el análisis multivariado, la DD, de acuerdo con las guías del 2009, persistió como predictor independiente de RVP > 1,400 mmHg.min.l-1. Conclusión: Las guías del 2016 reducen la prevalencia de DD. Ésta, tanto en las guías del 2009 como en las del 2106, fue predictor univariado de DAS < 0.60 ml.mmHg-1 y RVP > 1,400 mmHg.min.l-1. La DD, de acuerdo con las guías de 2009, resultó predictora independiente de RVP > 1,400 mmHg.min.l-1.

Abstract Objectives: To assess the prevalence of developmental disabilities (DD) according to the criteria of the 2009 and 2016 guidelines, and its association with systemic arterial compliance (DAS) and peripheral vascular resistance (RVP). Material and methods: 306 patients aged ≥ 40 years, with ejection fraction ≥ 50% were analyzed. It was estimated in all DAS and RVP. Results: The prevalence of DD was 32.7% and 22.9% according to the 2009 and 2016 guidelines, respectively (p ≤ 0.0001). Patients with DD according to the 2009 guideline had a lower average of DAS than those with normal function (p = 0.0001). Similar with the 2016 guide (p = 0.0007). The presence of DD according to the 2009 and 2016 guideline showed higher RVP values than normal values (p = 0.005 and p = 0.018, respectively). The DD according to both guidelines was a predictor, in the univariate analysis, of DAS < 0.60 ml.mmHg−1 and RVP > 1400 mmHg.min.l−1. The DD according to the 2009 guideline persisted as an independent predictor, in the multivariate analysis, of RVP > 1400 mmHg.min.l−1. Conclusion: The 2016 guide decreases the prevalence of DD. The DD, both from the 2009 and 2106 guidelines, were univariate predictors of DAS <0.60 ml.mmHg−1 and RVP > 1400 mmHg.min.l−1. The DD according to the 2009 guide, was an independent predictor of RVP > 1400 mmHg.min.l−1.

Efectos clínicos de la corrección del valor de la fracción de expulsión del ventrículo izquierdo en pacientes con insuficiencia valvular mitral / Clinical impact of the correction of the value of left ventricular ejection fraction in patients with mitral valve regurgitation

Resumen Introducción y objetivos: La insuficiencia valvular mitral provoca el vaciado simultáneo hacia la aorta y la aurícula izquierda durante la sístole ventricular, lo que produce una disminución del volumen hacia la circulación sistémica. En este estudio se busca obtener un dato preciso del porcentaje de volumen expulsado en sentido anterógrado en pacientes con insuficiencia mitral. Métodos: Se aplica una fórmula ecocardiográfica de “corrección” de la fracción de expulsión del ventrículo izquierdo (FEVI) en 114 pacientes con insuficiencia mitral, con base en la medición de la fracción regurgitante. Resultados: La corrección de la FEVI demostró que el 44.7% de los casos (n = 51) debe reclasificarse en cuanto a la calidad de su función sistólica ventricular izquierda. De 79 sujetos con FEVI normal (≥ 50%) sólo se mantuvieron 32 en la misma categoría; en el grupo con FEVI moderadamente reducida (intervalo intermedio, 40-49.9%) se pasó de 6 a 23 casos y, en aquéllos con FEVI reducida (< 40%), el grupo aumentó de 29 a 59; el subgrupo de pacientes con FEVI < 30% se incrementó de 21 a 41 sujetos. Conclusiones: Puesto que en la mayoría de las guías de tratamiento la FEVI se usa para estratificar riesgos e indicaciones terapéuticas, los autores creen que la ponderación de la insuficiencia mitral puede incrementar la precisión del tratamiento y la posibilidad de incluir a pacientes que no están considerados en esos tratamientos en el momento actual.

Abstract Introduction and objectives: Mitral valve regurgitation causes simultaneous emptying to the aorta and left atrium during ventricular systole, generating a decrease in volume supply to the systemic circulation. In this study we seek to obtain an accurate data on the percentage of volume expelled in the anterograde direction in patients with mitral regurgitation. Methods: An echocardiographic formula for “correction” of the left ventricular ejection fraction (LVEF) was applied in 114 patients with mitral regurgitation, based on the measurement of the regurgitant fraction. Results: Correction of the LVEF showed that 44.7% of cases (n = 51) should be reclassified in terms of the quality of their left ventricular systolic function. Of 79 subjects with normal LVEF (≥ 50%) only 32 remained in the same category; in the group with moderately reduced LVEF (medium range, 40-49.9%) it went from 6 to 23 cases and, in those with reduced LVEF (< 40%), the group increased from 29 to 59; the subgroup of patients with LVEF < 30% increased from 21 to 41 subjects. Conclusions: Given that in most treatment guidelines LVEF is used to stratify risks and therapeutic indications, the authors believe that the weighting of mitral regurgitation can increase the accuracy of treatment, and the possibility of including patients who, at this current moment, are not considered for these therapies.

Prognostic Prediction of Cardiopulmonary Exercise Test Parameters in Heart Failure Patients with Atrial Fibrillation / Previsão Prognóstica dos Parâmetros do Teste de Esforço Cardiopulmonar em Pacientes com Insuficiência Cardíaca e Fibrilação Atrial

Abstract Background: Atrial fibrillation (AF) is associated with increased mortality in heart failure (HF) patients. Objective: To evaluate whether the risk of AF patients can be precisely stratified by relation with cardiopulmonary exercise test (CPET) cut-offs for heart transplantation (HT) selection. Methods: Prospective evaluation of 274 consecutive HF patients with left ventricular ejection fraction ≤ 40%. The primary endpoint was a composite of cardiac death or urgent HT in 1-year follow-up. The primary endpoint was analysed by several CPET parameters for the highest area under the curve and for positive (PPV) and negative predictive value (NPV) in AF and sinus rhythm (SR) patients to detect if the current cut-offs for HT selection can precisely stratify the AF group. Statistical differences with a p-value <0.05 were considered significant. Results: There were 51 patients in the AF group and 223 in the SR group. The primary outcome was higher in the AF group (17.6% vs 8.1%, p = 0.038). The cut-off value of pVO2 for HT selection showed a PPV of 100% and an NPV of 95.5% for the primary outcome in the AF group, with a PPV of 38.5% and an NPV of 94.3% in the SR group. The cut-off value of VE/VCO2 slope showed lower values of PPV (33.3%) and similar NPV (92.3%) to pVO2 results in the AF group. Conclusion: Despite the fact that AF carries a worse prognosis for HF patients, the current cut-off of pVO2 for HT selection can precisely stratify this high-risk group.

Resumo Fundamento: A fibrilação atrial (FA) está associada ao aumento da mortalidade em pacientes com insuficiência cardíaca (IC). Objetivo: Avaliar se o risco de pacientes com FA pode ser estratificado com precisão em relação aos pontos de corte do teste de esforço cardiopulmonar (TECP) para seleção do transplante cardíaco (TC). Métodos: Avaliação prospectiva de 274 pacientes consecutivos com IC com fração de ejeção do ventrículo esquerdo ≤ 40%. O endpoint primário foi um composto de morte cardíaca ou TC urgente no seguimento de 1 ano. O endpoint primário foi analisado através de vários parâmetros do TECP para a maior área sob a curva e para o valor preditivo positivo (VPP) e negativo (VPN) em pacientes com FA e ritmo sinusal (RS) para detectar se os atuais pontos de corte para a seleção de TC podem estratificar com precisão o grupo com FA. Diferenças estatísticas com valor de p < 0,05 foram consideradas significativas. Resultados: Havia 51 pacientes no grupo de FA e 223 no grupo RS. O endpoint primário foi maior no grupo FA (17,6% vs. 8,1%, p = 0,038). O valor de corte de pVO2 para a seleção do TC mostrou um VPP de 100% e um VPN de 95,5% para o endpoint primário no grupo FA, com um VPP de 38,5% e um VPN de 94,3% no grupo RS. O valor de corte da inclinação VE/VCO2 apresentou valores mais baixos de VPP (33,3%) e valor semelhante de VPN (92,3%) aos resultados de pVO2 no grupo FA. Conclusões: Apesar do fato de a FA apresentar um pior prognóstico para os pacientes com IC, o atual ponto de corte de pVO2 para a seleção de TC pode estratificar com precisão esse grupo de alto risco.

Decompensated Heart Failure with Mid-Range Ejection Fraction: Epidemiology and In-Hospital Mortality Risk Factors

Abstract Background: Recently, a new HF entity, with LVEF between 40-49%, was presented to comprehend and seek better therapy for HF with preserved LVEF (HFpEF) and borderline, in the means that HF with reduced LVEF (HFrEF) already has well-defined therapy in the literature. Objective: To compare the clinical-therapeutic profile of patients with HF with mid-range LVEF (HFmrEF) with HFpEF and HFrEF and to verify predictors of hospital mortality. Method: Historical cohort of patients admitted with decompensated HF at a supplementary hospital in Recife/PE between April/2007 - August/2017, stratified by LVEF (< 40%/40 - 49/≥ 50%), based on the guideline of the European Society of Cardiology (ESC) 2016. The groups were compared and Logistic Regression was used to identify predictors of independent risk for in-hospital death. Results: A sample of 493 patients, most with HFrEF (43%), HFpEF (30%) and HFmrEF (26%). Average age of 73 (± 14) years, 59% men. Hospital mortality 14%, readmission within 30 days 19%. In therapeutics, it presented statistical significance among the 3 groups, spironolactone, in HFrEF patients. Hospital death and readmission within 30 days did not make difference. In the HFmrEF group, factors independently associated with death were: valve disease (OR: 4.17, CI: 1.01-9.13), altered urea at admission (OR: 6.18, CI: 1.78-11.45) and beta-blocker hospitalization (OR: 0.29, CI: 0.08-0.97). In HFrEF, predictors were: prior renal disease (OR: 2.84, CI: 1.19-6.79), beta-blocker at admission (OR: 0.29, CI: 0.12-0.72) and ACEI/ ARB (OR: 0.21, CI: 0.09-0.49). In HFpEF, only valve disease (OR: 4.61, CI: 1.33-15.96) and kidney disease (OR: 5.18, CI: 1.68-11.98) were relevant. Conclusion: In general, HFmrEF presented intermediate characteristics between HFrEF and HFpEF. Independent predictors of mortality may support risk stratification and management of this group.

Heart failure with preserved ejection fraction: an update on pathophysiology, diagnosis, treatment, and prognosis

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have symptoms and signs of HF with normal or near-normal left ventricular ejection fraction (LVEF ≥50%). Roughly half of all patients with HF worldwide have an LVEF ≥50% and nearly half have an LVEF <50%. Thanks to the increased scientific attention about the condition and improved characterization and diagnostic tools, the incidence of HF with reduced ejection fraction (HFrEF) dropped while that of HFpEF has increased by 45%. HFpEF has no single guideline for diagnosis or treatment, the patient population is heterogeneously and inconsistently described, and longitudinal studies are lacking. To better understand and overcome the disease, in this review, we updated the latest knowledge of HFpEF pathophysiology, introduced the existing promising diagnostic methods and treatments, and summarized its prognosis by reviewing the most recent cohort studies.

Insuficiencia cardíaca con fracción de expulsión preservada: el lado oscuro de una vieja enfermedad / Heart failure with preserved ejection fraction: the dark side of an old disease

Resumen La insuficiencia cardíaca (IC) es un problema de salud pública global con más de 37 millones de individuos afectados en el mundo. La insuficiencia cardíaca con fracción de expulsión preservada (ICFEp) representa una categoría cada vez más frecuente en la práctica clínica, constituye hasta el 60% de los casos y presenta diferencias importantes en el diagnóstico y tratamiento en comparación con la insuficiencia cardíaca y la fracción de expulsión reducida. Esta revisión de ICFEp expone la epidemiología, delimita los principales factores de riesgo y mecanismos fisiopatológicos, identifica las características clínicas/paraclínicas y los criterios diagnósticos, y finaliza con un llamado para realizar investigación en este país.

Abstract Heart failure is a global public health problem, with more than 37 million patients living with heart failure around the world. Heart failure with preserved ejection fraction is an increasingly common category (approximately 60% of the cases) and shows remarkable differences in diagnosis and treatment when compared with heart failure with reduced ejection fraction. The current review covers epidemiology, risk factors, pathophysiologic mechanisms, clinical and paraclinical characteristics and diagnostic criteria of heart failure with preserved ejection fraction and concludes with a plea for original research in our country.

Strain Analysis of Left Ventricular Function in the Association of Hypertrophic Cardiomyopathy and Systemic Arterial Hypertension / Avaliação da Função Ventricular Esquerda na Associação de Cardiomiopatia Hipertrófica e Hipertensão Arterial Sistêmica pela Técnica de Strain

Abstract Background: Hypertrophic cardiomyopathy (HCM) is the most common heart disease of genetic origin in the world population, with a prevalence of at least 1/500. The association with systemic arterial hypertension (SAH) is not uncommon, as it affects approximately 25% of the world population. Most studies aim at the differential diagnosis between these diseases, but little is known about the magnitude of this association. Objective: To compare left ventricular global longitudinal strain (GLS) in HCM patients with and without associated SAH. Methods: Retrospective cross-sectional study that included 45 patients with HCM and preserved ejection fraction, with diagnosis confirmed by magnetic resonance imaging, including 14 hypertensive patients. Transthoracic echocardiography was performed, with emphasis on left ventricular myocardial strain analysis using GLS. In this study, p < 0.05 was considered statistically significant. Results: Left ventricular strain was significantly lower in hypertensive individuals compared to normotensive individuals (-10.29 ± 2.46 vs. -12.35% ± 3.55%, p = 0.0303), indicating greater impairment of ventricular function in that group. Mean age was also significantly higher in hypertensive patients (56.1 ± 13.9 vs. 40.2 ± 12.7 years, p = 0.0001). Diastolic dysfunction was better characterized in hypertensive patients (p = 0.0242). Conclusion: Myocardial strain was significantly lower in the group of patients with HCM and SAH, suggesting greater impairment of ventricular function. This finding may be related to a worse prognosis with early evolution to heart failure. Prospective studies are required to confirm this hypothesis.

Resumo Fundamentos: A cardiomiopatia hipertrófica (CMH) é a doença cardíaca de origem genética mais frequente na população mundial, com prevalência de, pelo menos, 1/500. A associação com hipertensão arterial sistêmica (HAS) não é incomum, uma vez que esta acomete aproximadamente 25% da população mundial. A maioria dos estudos objetiva o diagnóstico diferencial entre essas doenças, mas pouco se sabe sobre a magnitude dessa associação. Objetivo: Comparar o strain longitudinal global (SLG) do ventrículo esquerdo em pacientes portadores de CMH com e sem HAS associada. Métodos: Estudo transversal retrospectivo que incluiu 45 pacientes portadores de CMH e fração de ejeção preservada, com diagnóstico confirmado por ressonância magnética, sendo 14 hipertensos. Realizada avaliação ecocardiográfica transtorácica com ênfase na análise da deformação miocárdica do ventrículo esquerdo por meio do SLG. Valores de p < 0,05 foram considerados estatisticamente significativos. Resultados: A deformação do ventrículo esquerdo foi significativamente menor nos hipertensos quando comparada aos normotensos (-10,29 ± 2,46 vs. -12,35% ± 3,55%, p = 0,0303), indicando maior comprometimento da função ventricular naquele grupo. A média de idade também foi significativamente maior nos hipertensos (56,1 ± 13,9 vs. 40,2 ± 12,7 anos, p = 0,0001). A disfunção diastólica foi melhor caracterizada nos pacientes hipertensos (p = 0,0242). Conclusão: A deformação miocárdica foi significativamente menor no grupo de pacientes com CMH e HAS, sugerindo maior comprometimento da função ventricular. Esse achado pode estar relacionado a um pior prognóstico com evolução precoce para insuficiência cardíaca. Estudos prospectivos são necessários para confirmar essa hipótese.

The Use of Two-Dimensional Strain Measured by Speckle Tracking in the Identification of Incipient Ventricular Dysfunction in HIV-Infected Patients on Antiretroviral Therapy, Untreated HIV Patients and Healthy Controls / O Uso do Strain Bidimensional Obtido pelo Speckle Tracking na Identificação da Disfunção Ventricular Incipiente em Pacientes Infectados pelo HIV em Uso de Terapia Antirretroviral, Pacientes HIV não Tratados e Controles Saudáveis

Abstract Background: Most cardiovascular abnormalities in patients infected with the human immunodeficiency virus (HIV) have been associated with myocardial damage directly caused by the virus. Some cases, however, may be associated with adverse effects from antiretroviral therapy (ART). New ventricular function assessment techniques are capable of detecting early changes in the cardiac function of HIV-infected patients using or not using ART. The usefulness of these techniques has been little employed in these patients. Objectives: To investigate the potential influence of antiretroviral therapy (ART) on the occurrence of subclinical left ventricular systolic dysfunction evaluated by myocardial strain rate analysis using two-dimensional speckle tracking echocardiography (2-D Echo) in treated HIV patients compared to untreated patients and healthy individuals. Methods: Sixty-eight HIV-infected patients with no cardiovascular symptoms, normal left ventricular (LV) ejection fraction (> 0.55 on 2-D Echo) were divided into three groups: 11 patients not using antiretroviral therapy (NT), 24 using protease inhibitor (PI) and 33 using non-nucleoside reverse transcriptase inhibitor (NNRTI). We also studied 30 normal non-HIV infected individuals (Ctrl). Demographic, clinical, biochemical and anthropometric data were collected. Preliminary transthoracic echocardiography included study of myocardial strain using two-dimensional speckle tracking. We studied strain and strain rate in the seventeen left ventricular (LV) myocardial segments in the longitudinal, circumferential and radial axes. Statistical analysis of the data was done with IBM SPSS - version 20 for Windows. Upon analysis of the data, namely the normality of independent variables in the different groups and the homogeneity of the variances between the groups, Kruskal-Wallis' non-parametric test was done, followed by Dunn's multiple comparison tests to test the significance of the differences between the values measured in the study groups. A significance level of 5% was adopted for decision-making on statistical tests. Results: The mean age of HIV patients was 40 ± 8.65 years and the mean age of controls was 50 ± 11.6 years (p < 0.001). Median LV global longitudinal strain (GLS) of NT patients (-17.70%), PI patients (-18.27%) and NNRTIs (-18.47%) were significantly lower than that of the Ctrl group (-20.77%; p = 0.001). There was no significant difference in mean SLG between treated patients (PI, NNRTI) and untreated (NT) patients. No significant differences were observed in mean circumferential and radial strain, nor on circumferential and radial strain rates between the NT, PI, NNRTI and Ctrl groups. Conclusion: The data suggest that HIV patients present, on myocardial strain measured by speckle tracking, signs of early LV systolic dysfunction that seem to be unrelated to the presence of ART. The prognostic significance of this condition in these patients deserves further studies.

Resumo Fundamento: A maior parte das alterações cardiovasculares dos pacientes infectados pelo vírus da imunodeficiência humana (HIV) tem sido associada ao dano miocárdico causado diretamente pelo vírus. Alguns casos, porém, podem estar associados a efeitos adversos da terapia antirretroviral (TARV). Novas técnicas de avaliação da função ventricular são capazes de detectar modificações precoces na função cardíaca do paciente infectado pelo HIV em uso ou não de TARV. A utilidade dessas técnicas tem sido pouco empregada nesses pacientes. Objetivos: Investigar possível influência da terapia antirretroviral (TARV) na ocorrência de disfunção sistólica ventricular esquerda subclínica avaliada pela análise da taxa de deformação miocárdica (strain) por meio do speckle tracking ao ecocardiograma bidimensional (E2D) em pacientes portadores do HIV tratados, comparados com pacientes não tratados e indivíduos saudáveis. Métodos: Sessenta e oito pacientes infectados pelo HIV assintomáticos do ponto de vista cardiovascular, com fração de ejeção do ventrículo esquerdo (VE) normal (>0,55 pelo E2D) foram divididos em três grupos: 11 pacientes sem tratamento antirretroviral (ST), 24 em uso de inibidor de protease (IP) e 33 em uso de inibidor de transcriptase reversa não nucleosídeo (ITRNN). Foram estudados também 30 indivíduos normais não infectados pelo HIV (Ctrl). Foram coletados dados demográficos, clínicos, bioquímicos e antropométricos. A ecocardiografia transtorácica foi realizada incluindo no estudo inicial o estudo da deformação miocárdica pela técnica bidimensional (speckle tracking). Estudamos o strain e a sua taxa de deformação (strain rate) nos dezessete segmentos miocárdicos do ventrículo esquerdo (VE) nos eixos longitudinal, circunferencial e radial. A análise estatística dos dados foi feita com o programa IBM SPSS - versão 20 para Windows. Depois de analisados os dados, nomeadamente a normalidade das variáveis independentes nos diferentes grupos e a homogeneidade das variâncias entre os grupos, decidiu-se utilizar o teste não paramétrico de Kruskal-Wallis seguido dos testes de comparações múltiplas pelo procedimento de Dunn, para testar a significância das diferenças entre os valores medidos nos grupos em estudo. Foi considerado o nível de significância de 5% para a tomada de decisão nos testes estatísticos realizados. Resultados: A média das idades dos pacientes com HIV foi de 40 ± 8,65 anos e a idade média dos controles foi de 50 ± 11,6 anos (p < 0,001). Os valores medianos do strain longitudinal global do VE (SLG) dos pacientes ST (-17.70%), dos pacientes IP (-18.27%) e ITRNN (-18.47%) foram significativamente menores do que o grupo Ctrl (-20,77%; p = 0,001). Não houve diferença significante nos valores médios do SLGentre os pacientes tratados (IP, ITRNN) e não tratados (ST). Não foram observadas diferenças significantes nos valores médios do strain circunferencial e radial, nem nas taxas de deformação circunferencial e radial entre os grupos ST, IP, ITRNN e Ctrl. Conclusão: Os dados sugerem que pacientes com HIV apresentam, à análise da deformação miocárdica ao speckle tracking, sinais de disfunção sistólica incipiente do VE que parece não ter relação com a presença de TARV. O significado prognóstico dessa alteração nesses pacientes merece estudos futuros.

The relationship between mitral annular calcification, metabolic syndrome and thromboembolic risk

Abstract Introduction: Metabolic syndrome (MetS) is defined as an association between diabetes, hypertension, obesity and dyslipidemia and an increased risk of cardiovascular disease. Mitral annular calcification (MAC) is associated with several cardiovascular disorders, including coronary artery disease, atrial fibrillation (AF), heart failure, ischemic stroke and increased mortality. The CHA2DS2-VASc score is used to estimate thromboembolic risk in AF. However, the association among MAC, MetS and thromboembolic risk is unknown and was evaluated in the current study. Methods: The study group consisted of 94 patients with MAC and 86 patients with MetS. Patients were divided into two groups: those with and those without MAC. Results: Patients with MAC had a higher MetS rate (P<0.001). In patients with MAC, the CHA2DS2-VASc scores and the rate of cerebrovascular accident and AF were significantly higher compared to those without MAC (P<0.001, for both parameters). The results of the multivariate regression analysis showed that history of smoking, presence of MetS and high CHA2DS2-VASc scores were associated with the development of MAC. ROC curve analyses showed that CHA2DS2-VASc scores were significant predictors for MAC (C-statistic: 0.78; 95% CI: 0.706-0.855, P<0.001). Correlation analysis indicated that MAC was positively correlated with the presence of MetS and CHA2DS2-VASc score (P=0.001, r=0.264; P<0.001, r=0.490). Conclusion: We have shown that CHA2DS2-VASc score and presence of MetS rates were significantly higher in patients with MAC compared without MAC. Presence of MAC was correlated with CHA2DS2-VASc score, presence of MetS, AF and left atrial diameter and negatively correlated with left ventricular ejection fraction.

Global Longitudinal Strain Predicts Poor Functional Capacity in Patients with Systolic Heart Failure / Strain Longitudinal Global é Preditor de Baixa Capacidade Funcional em Pacientes com Insuficiência Cardíaca Sistólica

Abstract Background: Left ventricular global longitudinal strain value (GLS) can predict functional capacity in patients with preserved left ventricular ejection fraction (LVEF) heart failure (HF) and to assess prognosis in reduced LVEF HF. Objetive: Correlate GLS with parameters of Cardiopulmonary Exercise Test (CPET) and to assess if they could predict systolic HF patients that are more appropriated to be referred to heart transplantation according to CPET criteria. Methods: Systolic HF patients with LVEF < 45%, NYHA functional class II and III, underwent prospectively CPET and echocardiography with strain analysis. LVEF and GLS were correlated with the following CPET variables: maxVO2, VE/VCO2 slope, heart rate reduction during the first minute of recovery (HRR) and time needed to reduce maxVO2 in 50% after physical exercise (T1/2VO2). ROC curve analysis of GLS to predict VO2 < 14 mL/kg/min and VE/VCO2 slope > 35 (heart transplantation's criteria) was performed. Results: Twenty six patients were selected (age, 47 ± 12 years, 58% men, mean LVEF = 28 ± 8%). LVEF correlated only with maxVO2 and T1/2VO2. GLS correlated to all CPET variables (maxVO2: r = 0.671, p = 0.001; VE/VCO2 slope: r = -0.513, p = 0.007; HRR: r = 0.466, p = 0.016, and T1/2VO2: r = -0.696, p = 0.001). GLS area under the ROC curve to predict heart transplantation's criteria was 0.88 (sensitivity 75%, specificity 83%) for a cut-off value of -5.7%, p = 0.03. Conclusion: GLS was significantly associated with all functional CPET parameters. It could classify HF patients according to the functional capacity and may stratify which patients have a poor prognosis and therefore to deserve more differentiated treatment, such as heart transplantation.

Resumo Fundamento: O strain longitudinal global (SLG) é capaz de predizer a capacidade funcional dos pacientes com insuficiência cardíaca (IC) e fração de ejeção do ventrículo esquerdo (FEVE) preservada, e avaliar o prognóstico na IC com FEVE reduzida. Objetivo: Correlacionar o SLG com parâmetros do teste de exercício cardiopulmonar (TECP), e avaliar se o SLG seria capaz de predizer quais pacientes com IC sistólica deveriam ser encaminhados ao transplante cardíaco de acordo com os critérios do TECP. Métodos: Os pacientes com IC sistólica com FEVE <45%, classe funcional NYHA II e III, submeteram-se prospectivamente ao TECP e à ecocardiografia com análise do strain. A FEVE e o SLG foram correlacionados com as seguintes variáveis do TECP: maxVO2, inclinação de VE/VCO2, redução da frequência cardíaca durante o primeiro minuto de recuperação (RFC), e tempo necessário para a redução do maxVO2 em 50% após o exercício físico (T1/2VO2). Foi realizada análise da curva ROC do SLG em predizer um VO2 < 14 mL/kg/min e uma inclinação de VE/VCO2 > 35 (critérios para transplante cardíaco). O nível de significância adotado na análise estatística foi de p < 0,05. Resultados: Vinte e seis pacientes foram selecionados para o estudo (idade, 47±12 anos, 58% homens, FEVE média LVEF = 28 ± 8%). A FEVE correlacionou-se somente com o maxVO2 e o T1/2VO2. O SLG correlacionou-se com todas as variáveis do TECP (maxVO2: r = 0,671; p = 0,001; inclinação de VE/VCO2: r = -0,513; p = 0,007; RFC: r = 0,466; p = 0,016; e T1/2VO2: r = -0,696, p = 0,001). A área sob a curva ROC para o SLG para predizer os critérios para transplante cardíaco foi de 0,88 (sensibilidade 75%, especificidade 83%) para um ponto de corte de -5,7%, p = 0,03. Conclusão: O SLG apresentou associação significativa com todos os parâmetros funcionais do TECP. O SLG foi capaz de classificar os pacientes com IC segundo capacidade funcional e possivelmente pode identificar quais pacientes têm um prognóstico ruim e, portanto, se beneficiariam de um tratamento diferenciado, tal como o transplante cardíaco.

Presystolic Wave is Associated with Subclinical Left Ventricular Dysfunction Assessed by Myocardial Performance Index in Type 2 Diabetes Mellitus / Onda Pressistólica Associada à Disfunção Ventricular Esquerda Subclínica e Avaliada com Base no Índice de Performance Miocárdica em Pacientes com Diabetes Mellitus Tipo 2

Abstract Background: Myocardial performance index (MPI), demonstrates both systolic and diastolic functions of the left ventricle. Presystolic wave (PSW) is frequently detected on Doppler examination of the left ventricular outflow tract and possible mechanism of PSW is impaired LV compliance and left ventricular stiffness. Objective: To investigate the relationship between PSW and MPI in type 2 diabetic patients. Method: A total of 129 type 2 diabetic patients were included in this study. Patients were divided into two groups according to the presence of PSW on Doppler echocardiography. There were 90 patients (38 male, mean age 57.77 ± 10.91 years) in the PSW-positive group and 39 patients (13 male; mean age: 55.31 ± 11.29 years) in the PSW-negative group. The p values of < 0.05 were considered statistically significant. Results: MPI was higher in PSW- positive group (0.63 ± 0.17vs 0.52 ± 0.13, p < 0.001). In addition, subclinical left ventricle dysfunction (LVD) was higher in the PSW- positive group (p = 0.029). Univariate analysis showed that the presence of PSW associated with abnormal MPI (p = 0.031). Pearson correlation analysis showed that PSW velocity correlated with MPI (r: 0.286, p = 0.006). Conclusion: Presence of the PSW on Doppler examination was associated with subclinical LV dysfunction in patients with DM type 2. This easy-to-perform echocardiographic parameter may be related to subclinical LVD among patients with type 2 DM.

Resumo Fundamento: O índice de performance miocárdica (IPM) avalia as funções sistólica e diastólica do ventrículo esquerdo. A onda pressistólica (OPS) é geralmente detectada no exame Doppler da via de saída do ventrículo esquerdo e seus possíveis mecanismos são complacência prejudicada e rigidez do ventrículo esquerdo. Objetivo: Investigar a relação entre OPS e IPM em pacientes com diabetes tipo 2. Método: 129 pacientes com diabetes tipo 2 foram incluídos no estudo. Os sujeitos foram alocados em dois grupos, com base na presença de OPS no exame ecocardiográfico com Doppler. Foram incluídos 90 pacientes (38 homens, idade média 57,77 ± 10,91 anos) no grupo OPS-positiva e 39 pacientes (13 homens; idade média 55,31 ± 11,29 anos) no grupo OPS-negativa. Valor de p < 0,05 foi considerado para significância estatística. Resultados: O IPM foi mais alto no grupo OPS-positiva (0,63 ± 0,17 vs 0,52 ± 0,13, p < 0,001). Além disso, a disfunção ventricular esquerda subclínica (DVE) foi maior no grupo OPS-positiva (p = 0,029). Análise univariada mostrou associação de OPS com IPM anormal (p = 0,031), assim como o coeficiente de correlação de Pearson mostrou correlação entre velocidade de OPS e IPM (r: 0,286, p = 0,006). Conclusão: Presença de OPS na ecocardiografia com Doppler foi associada à DVE subclínica em pacientes com diabetes tipo 2. Esse exame ecocardiográfico de fácil execução pode ser relacionado à DVE subclínica entre pacientes com diabetes tipo 2.

Heart Failure with Mid-Range Ejection Fraction - State of the Art / Insuficiência Cardíaca com Fração de Ejeção Intermediária - Estado da Arte

Abstract In 2016, the European Society of Cardiology (ESC) recognized heart failure (HF) with ejection fraction between 40 and 49% as a new HF phenotype, HF with mid-range ejection fraction (HFmrEF), with the main purpose of encouraging studies on this new category. In 2018, the Brazilian Society of Cardiology adhered to this classification and introduced HFmrEF in Brazil. This paper presents a narrative review of what the literature has described about HFmrEF. The prevalence of patients with HFmrEF ranged from 13 to 24% of patients with HF. Analyzing the clinical characteristics, HFmrEF shows intermediate characteristics or is either similar to HF with preserved ejection fraction (HFpEF) or to HF with reduced fraction (HFrEF). Regarding the prognosis, HFmrEF's all-cause mortality is similar to HFpEF's and lower than HFrEF's. Studies that analyzed cardiac mortality concluded that there was no significant difference between HFmrEF and HFrEF, both of which were lower than HFpEF. Despite the significant increase of publications on HFmrEF, there is a great scarcity of prospective studies and clinical trials that allow delineating specific therapies for this new phenotype. To better treat HFmrEF patients, it is fundamental that cardiologists and internists understand the differences and similarities of this new phenotype.

Resumo Em 2016, a Sociedade Europeia de Cardiologia (ESC) reconheceu a insuficiência cardíaca (IC) com fração de ejeção do ventrículo esquerdo entre 40% e 49% como um novo fenótipo de IC, a IC com fração de ejeção intermediária (ICFEI), tendo como principal intuito, incentivar estudos sobre essa nova categoria. Em 2018, a Sociedade Brasileira de Cardiologia aderiu a essa classificação e introduziu a ICFEI no Brasil. O presente trabalho traz uma revisão narrativa sobre o que a literatura descreve até o momento sobre ICFEI. A prevalência de pacientes com ICFEI variou de 13-24% dos pacientes com IC. Quando avaliadas as características clínicas, a ICFEI apresenta um caráter intermediário ou se assemelha algumas vezes com a IC de fração de ejeção preservada (ICFEP) e outras com a IC de fração reduzida (ICFER). Quanto ao prognóstico, a ICFEI apresenta mortalidade por todas as causas semelhante a ICFEP e menor que a ICFER. Os estudos que analisaram a mortalidade por causa cardíaca concluíram que não houve diferença significativa entre ICFEI e ICFER, sendo ambas menores que a ICFEP. Apesar do considerável aumento de publicações sobre a ICFEI, ainda existe uma grande carência de estudos prospectivos e ensaios clínicos que possibilitem delinear terapias específicas para esse novo fenótipo. O conhecimento das particularidades da ICFEI por cardiologistas e internistas é fundamental para o melhor manejo desses pacientes.

Is hepatojugular reflux a good predictor of heart failure with preserved ejection fraction?

SUMMARY Hypertension may occur with left ventricular (LV) diastolic dysfunction, and the consequence may be symptoms and signs of heart failure (HF). Hepatojugular reflux (HJR), described as a sign of regurgitation of the tricuspid valve, may reflect structural and functional changes of the LV in the hypertensive patient. The signal may be present in the presence of HF. Case: male, 49 years old with uncontrolled blood pressure. Physical examination showed jugular turgescence, HJR, and elevated blood pressure. Complementary exams showed signs of atrial and left ventricular overload in the electrocardiogram and, the echocardiogram showed left atrium volume increase, concentric LV hypertrophy and signs of grade I diastolic dysfunction. DISCUSSIO: The HJR present correlates with pulmonary artery pressure and probably reflect the increase in central blood volume.

RESUMO A hipertensão pode cursar com disfunção diastólica de ventrículo esquerdo (VE) e a consequência disso pode ser sintomas e sinais de insuficiência cárdica (IC). O refluxo hepatojugular (RHJ), descrito como sinal de regurgitação da valva tricúspide, pode refletir alterações estruturais e funcionais do VE no paciente hipertenso. O sinal pode estar presente na vigência de IC. Caso: homem, 49 anos compressão arterial não controlada. Ao exame físico apresentou turgência jugular, RHJ e pressão arterial elevada. Os exames complementares mostraram sinais de sobrecarga atrial e de ventrículo esquerdo no eletrocardiograma, e no ecocardiograma foi evidenciado aumento do volume do átrio esquerdo, hipertrofia concêntrica do VE e sinais de disfunção diastólica grau I. DISCUSSÃO: RHJ presente correlaciona-se com a pressão da artéria pulmonar e provavelmente reflete o aumento do volume sanguíneo central.