Representativeness in randomised clinical trials supporting acute coronary syndrome guidelines.

AIMS: Clinical practice guidelines (CPGs) are published to guide the management of acute coronary syndrome (ACS). We aimed to critically appraise the representativeness and standard of care of randomised clinical trials (RCTs) supporting CPGs for ACS. METHODS AND RESULTS: American and European CPGs for ST- and non-ST-elevation ACS were screened to extract all references (n = 2128) and recommendations (n = 600). Among the 407 primary publications of RCTs (19.1%), there were 52.6 and 73.2% recruiting patients in North America and Europe, respectively, whereas other regions were largely under-represented (e.g. 25.3% RCTs recruited in Asia). There was 68.6% RCTs enrolling patient with ACS, whereas the remaining 31.4% did not enrol any patient with ACS. There was under-representation of some important subgroups, including elderly, female (29.9%), and non-white patients (<20%). The incidence and type of reperfusion reported in these RCTs were not reflective of current clinical practice (the percentage of patients who underwent percutaneous coronary intervention (PCI) among all RCTs was 42.7%; whereas for ST-Elevation Myocardial Infarction patients, the number of participants who underwent fibrinolysis was 3.3-fold higher than those who underwent primary PCI). All-cause mortality in these RCTs was 11.9% in RCTs with a follow-up ≤ 1 year. CONCLUSION: Randomised clinical trials supporting CPGs for ACS are not fully representative of the diversity of the ACS population and their current standard of care. While some of these issues with representativeness may be explained by how evidence has been accrued over time, efforts should be made by trialists to ensure that the evidence supporting CPGs is representative of the wider ACS population.

New Variant in Placophilin-2 Gene Causing Arrhythmogenic Myocardiopathy.

INTRODUCTION: Arrhythmogenic cardiomyopathy (ACM) is an inherited disease characterized by progressive fibroadipose replacement of cardiomyocytes. Its diagnosis is based on imaging, electrocardiographic, histological and genetic/familial criteria. The development of the disease is based mainly on desmosomal genes. Knowledge of the phenotypic expression of each of these genes will help in both diagnosis and prognosis. The objective of this study is to describe the genotype-phenotype association of an unknown PKP2 gene variant in a family diagnosed with ACM. METHODS: Clinical and genetic study of a big family carrying the p.Tyr168* variant in the PKP2 gene, in order to demonstrate pathogenicity of this variant, causing ACM. RESULTS: Twenty-two patients (proband and relatives) were evaluated. This variant presented with high arrhythmic load at an early age, but without evidence of structural heart disease after 20 years of follow-up, with low risk in predictive scores. We demonstrate evidence of its pathogenicity. CONCLUSIONS: The p.Tyr168* variant in the PKP2 gene causes ACM with a high arrhythmic load and with an absence of structural heart disease. This fact emphasizes the value of knowing the phenotypic expression of each variant.

Factores que afectan al pronóstico de pacientes con síndrome de tako-tsubo. Respuesta / Factors impacting prognosis among patients with tako-tsubo syndrome. Response

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Síndrome de tako-tsubo en varones: infrecuente, pero con mal pronóstico / Tako-tsubo syndrome in men: rare, but with poor prognosis

Introducción y objetivos: El síndrome de tako-tsubo es un proceso patológico potencialmente grave durante la fase aguda. Simula un infarto de miocardio, sin que haya lesiones coronarias potencialmente responsables. El objetivo de este trabajo es analizar la evolución y el pronóstico de los pacientes con síndrome de tako-tsubo en función del sexo. Métodos: Se analizaron las características de los pacientes incluidos en el registro RETAKO durante los años 2003 a 2015, un registro multicéntrico en el que participaron 32 hospitales españoles. Resultados: De los 562 pacientes incluidos, 493 (87,7%) eran mujeres. El dolor torácico fue menos frecuente como síntoma inicial en los varones que en las mujeres (43 [66,2%] frente a 390 [82,8%]; p < 0,01). El pronóstico fue peor en los varones, con mayor mortalidad intrahospitalaria (3 [4,4%] frente a 1 [0,2%]; p < 0,01), duración más prolongada de ingreso en cuidados intensivos (4,2 ± 3,7 frente a 3,2 ± 3,2 días; p = 0,03) y mayor frecuencia de insuficiencia cardiaca grave (22 [33,3%] frente a 95 [20,3%]; p = 0,02). Sin embargo la aparición de obstrucción dinámica a nivel del tracto de salida del ventrículo izquierdo se observó exclusivamente en mujeres (39 [7,9%] frente a 0 [0,0%]; p = 0,02) y la incidencia de insuficiencia mitral funcional también fue mayor en ellas (52 [10,6%] frente a 2 [2,9%]; p = 0,04). Conclusiones: El síndrome de tako-tsubo es una enfermedad que muestra grandes diferencias en función del sexo en cuanto a su incidencia, presentación y evolución, con un peor pronóstico en los varones

Introduction and objectives: Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. Methods: We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. Results: Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). Conclusions: Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men

Significant mitral regurgitation worsens the prognosis and favors the decision of conservative treatment in octogenarians with severe symptomatic aortic stenosis.

INTRODUCTION: The coexistence of significant mitral regurgitation (MR) and severe aortic stenosis is prevalent, has a prognostic impact and makes treatment in the elderly population a complex issue. The aim of this study is to determine the prevalence of significant MR among a population of octogenarians and its influence on treatment and prognosis. METHODS: We used the data from PEGASO (Pronóstico de la Estenosis Grave Aórtica Sintomática del Octogenario), a prospective registry that consecutively included 928 patients aged ≥80 years with severe symptomatic aortic stenosis. RESULTS: The prevalence of significant MR was 8.5% (79 patients) and independently associated with the decision to treat conservatively (odds ratio = 2.28, 95% confidence interval: 1.31-3.95, p = 0.003). The group of patients with significant MR had higher overall mortality at 12 months follow-up (51.9% vs 25%, p < 0.001), which remained on division into subgroups based on the presence of comorbidities (Charlson<5: 49.2% vs 21.9%, p < 0.001; and Charlson ≥5: 62.5% vs 41.7%, p = 0.07). Within the group of patients in whom conservative treatment was performed, those with significant MR had higher mortality at one year (62.7% vs 35%, p < 0.001). MR was a significant independent predictor of overall mortality at 12-month follow-up (hazard ratio = 1.87, 95% confidence interval: 1.09-3.18, p = 0.022). CONCLUSIONS: Significant MR has a high prevalence and worsens the prognosis of octogenarian patients with severe symptomatic aortic stenosis, especially in patients with conservative treatment, independently of the existence of comorbidities.

Tako-tsubo Syndrome in Men: Rare, but With Poor Prognosis.

INTRODUCTION AND OBJECTIVES: Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. METHODS: We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. RESULTS: Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). CONCLUSIONS: Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

Interatrial block and atrial arrhythmias in centenarians: Prevalence, associations, and clinical implications.

BACKGROUND: Data are lacking on the characteristics of atrial activity in centenarians, including interatrial block (IAB). OBJECTIVE: The aim of this study was to describe the prevalence of IAB and auricular arrhythmias in subjects older than 100 years and to elucidate their clinical implications. METHODS: We studied 80 centenarians (mean age 101.4 ± 1.5 years; 21 men) with follow-ups of 6-34 months. Of these 80 centenarians, 71 subjects (88.8%) underwent echocardiography. The control group comprised 269 septuagenarians. RESULTS: A total of 23 subjects (28.8%) had normal P wave, 16 (20%) had partial IAB, 21 (26%) had advanced IAB, and 20 (25.0%) had atrial fibrillation/flutter. The IAB groups exhibited premature atrial beats more frequently than did the normal P wave group (35.1% vs 17.4%; P < .001); also, other measurements in the IAB groups frequently fell between values observed in the normal P wave and the atrial fibrillation/flutter groups. These measurements included sex preponderance, mental status and dementia, perceived health status, significant mitral regurgitation, and mortality. The IAB group had a higher previous stroke rate (24.3%) than did other groups. Compared with septuagenarians, centenarians less frequently presented a normal P wave (28.8% vs 53.5%) and more frequently presented advanced IAB (26.3% vs 8.2%), atrial fibrillation/flutter (25.0% vs 10.0%), and premature atrial beats (28.3 vs 7.0%) (P < .01). CONCLUSION: Relatively few centenarians (<30%) had a normal P wave, and nearly half had IAB. Our data suggested that IAB, particularly advanced IAB, is a pre-atrial fibrillation condition associated with premature atrial beats. Atrial arrhythmias and IAB occurred more frequently in centenarians than in septuagenarians.

Centenarians and their hearts: A prospective registry with comprehensive geriatric assessment, electrocardiogram, echocardiography, and follow-up.

BACKGROUND: Data on the cardiac characteristics of centenarians are scarce. Our aim was to describe electrocardiogram (ECG) and echocardiography in a cohort of centenarians and to correlate them with clinical data. METHODS: We used prospective multicenter registry of 118 centenarians (28 men) with a mean age of 101.5±1.7 years. Electrocardiogram was performed in 103 subjects (87.3%) and echocardiography in 100 (84.7%). All subjects underwent a follow-up for at least 6 months. RESULTS: Centenarians with abnormal ECG were less frequently females (72% vs 93%), had higher rates of previous consumption of tobacco (14% vs 0) and alcohol (24% vs 12%), and scored lower in the perception of health status (6.8±2.0 vs 8.3±6.8). Centenarians with significant abnormalities in echocardiography were less frequently able to walk 6 m (33% vs 54%). Atrial fibrillation/flutter was found in 27 subjects (26%). Mean left ventricular (LV) ejection fraction was 60.0±10.5%. Moderate or severe aortic valve stenosis was found in 16%, mitral valve regurgitation in 15%, and aortic valve regurgitation in 13%. Diastolic dysfunction was assessed in 79 subjects and was present in 55 (69.6%). Katz index and LV dilation were independently associated with the ability to walk 6 m. Age, Charlson and Katz indexes, and the presence of significant abnormalities in echocardiography were associated with mortality. CONCLUSIONS: Centenarians have frequent ECG alterations and abnormalities in echocardiography. More than one fifth has atrial fibrillation, and most have diastolic dysfunction. Left ventricular dilation was associated with the ability to walk 6 m. Significant abnormalities in echocardiography were associated with mortality.

Comorbidity and intervention in octogenarians with severe symptomatic aortic stenosis.

BACKGROUND: The benefit from intervention in elderly patients with symptomatic severe aortic stenosis (AS) and high comorbidity is unknown. Our aims were to establish the correlation between the Charlson comorbidity index and the prognosis of octogenarians with symptomatic sever AS and to identify patients who might not benefit from intervention. METHODS: We used the data from PEGASO (Pronóstico de la Estenosis Grave Aórtica Sintomática del Octogenario--Prognosis of symptomatic severe aortic stenosis in octogenarians), a prospective registry that included consecutively 928 patients aged ≥ 80 years with severe symptomatic AS. RESULTS: The mean Charlson comorbidity index was 3.0 ± 1.7, a total of 151 patients (16.3%) presented high comorbidity (index ≥ 5). Median survival was lower for patients with high comorbidity than for those without (16.7 ± 1.2 vs. 26.5 ± 0.6 months, p < 0.001). In patients without high comorbidity planned interventional management was clearly associated with prognosis (log rank p < 0.001), which was not the case in patients with high comorbidity (log rank p > 0.10). In multivariate analysis, the only variables that were independently associated with prognosis were planned medical management and Charlson index. Patients with high comorbidity presented non-cardiac death more frequently than those who had not (28.6% vs. 19.5%, p = 0.008). CONCLUSIONS: One sixth of octogenarians with symptomatic severe AS have very high comorbidity (Charlson index ≥ 5). These patients have a poor prognosis in the short term and do not seem to benefit from interventional treatment.

Update on ischemic heart disease and critical care cardiology.

This article summarizes the main developments reported in 2013 on ischemic heart disease, together with the most important innovations in the management of acute cardiac patients.

Actualización en cardiopatía isquémica y cuidados críticos cardiológicos / Update on ischemic heart disease and critical care cardiology

Se revisan los principales avances publicados en el año 2013 sobre cardiopatía isquémica, junto con las novedades más relevantes sobre el manejo de los pacientes cardiacos críticos (AU)

This article summarizes the main developments reported in 2013 on ischemic heart disease, together with the most important innovations in the management of acute cardiac patients (AU)

Actualización en cardiopatía isquémica y cuidados críticos cardiológicos / Update on ischemic heart disease and critical care cardiology

Se revisan los principales avances publicados en el año 2012 sobre cardiopatía isquémica, junto con las novedades más relevantes sobre manejo de los pacientes cardiacos críticos (AU)

This article summarizes the main developments reported during the year 2012 concerning ischemic heart disease, together with the most relevant innovations in the management of acute cardiac patients (AU)

Update on ischemic heart disease and critical care cardiology.

This article summarizes the main developments reported during the year 2012 concerning ischemic heart disease, together with the most relevant innovations in the management of acute cardiac patients.

Impacto del tipo de hospital en el tratamiento y evolución de los pacientes con síndrome coronario agudo sin elevación del ST / Influence of hospital type on treatment and prognosis in patients with non-ST elevation acute coronary syndrome

Introducción y objetivos. Las guías de práctica clínica del síndrome coronario agudo sin elevación del ST (SCASEST) no valoran la infraestructura hospitalaria y la facilidad de acceso a la sala de hemodinámica. Este estudio analiza la influencia del tipo de hospital, con o sin sala de hemodinámica, en la forma de tratamiento de pacientes con SCASEST y su posible impacto en el pronóstico a medio plazo. Métodos. El GYSCA es un registro multicéntrico (15 hospitales) que analiza la aplicación de las guías en pacientes con SCASEST: 6 con sala de hemodinámica (hospitales centrales) y 9 sin hemodinámica (hospitales comarcales). Se realizó seguimiento clínico al alta y a los 3 y a los 12 meses. Resultados. Se reclutó a 1.133 pacientes consecutivos; 599 (52,9%) en hospitales centrales y 534 (47,1%) en hospitales comarcales. El uso de intervenciones de clase I fue mayor en los centrales (aspirina, clopidogrel, bloqueadores beta, IECA y estatinas; p < 0,01) y se revascularizó a más pacientes durante la hospitalización (el 43 frente al 30%; p < 0,01). El número de pacientes de hospitales comarcales que reingresaron por SCASEST al año fue 5 veces mayor que en los centrales (el 12,8 frente al 2,3%; p < 0,01), y el tipo de hospital fue uno de los predictores de eventos. Conclusiones. Los pacientes que ingresan por SCASEST en hospitales que no disponen de sala de hemodinámica son tratados de forma menos invasiva y con un tratamiento farmacológico menos ajustado a lo recomendado en las guías. Junto con los conocidos factores predictivos del pronóstico, el tipo de hospital puede tener un impacto adicional en la evolución (AU)

Introduction and objectives. Clinical practice guidelines on non-ST-segment elevation acute coronary syndrome (NSTEACS) do not take either hospital infrastructure or the availability of a catheterization laboratory into account. The aim of this study was to determine the influence of hospital type, either with or without a catheterization laboratory, on treatment and medium-term prognosis in patients with NSTEACS. Methods. The GYSCA multicenter study (covering 15 hospitals) investigated the implementation of clinical practice guidelines in patients with NSTEACS at six hospitals with catheterization laboratories (i.e. tertiary-care hospitals; THs) and nine without (i.e. secondary-care hospitals; SHs). Patients were assessed clinically at hospital discharge and after 3 and 12 months. Results. In total, 1133 consecutive patients were recruited: 599 (52.9%) in THs and 534 (47.1%) in SHs. The use of specific class-I interventions (i.e. aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors and statins) was more common in THs (P < .01) and more patients in THs underwent revascularization while in hospital (43% vs. 30%; P < .01). The number of SH patients who were readmitted for NSTEACS at 1 year was 5-fold greater than the number of TH patients (12.8% vs. 2.3%; P < .01), and hospital type was a predictor of an adverse event. Conclusions. Patients admitted for NSTEACS to a hospital without a catheterization laboratory were managed less invasively and their drug treatment was less likely to have been modified to match guideline recommendations. In addition to other well-known prognostic factors, hospital type can also have an influence on patient outcomes (AU)

[Influence of hospital type on treatment and prognosis in patients with non-ST elevation acute coronary syndrome]. / Impacto del tipo de hospital en el tratamiento y evolución de los pacientes con síndrome coronario agudo sin elevación del ST.

INTRODUCTION AND OBJECTIVES: Clinical practice guidelines on non-ST-segment elevation acute coronary syndrome (NSTEACS) do not take either hospital infrastructure or the availability of a catheterization laboratory into account. The aim of this study was to determine the influence of hospital type, either with or without a catheterization laboratory, on treatment and medium-term prognosis in patients with NSTEACS. METHODS: The GYSCA multicenter study (covering 15 hospitals) investigated the implementation of clinical practice guidelines in patients with NSTEACS at six hospitals with catheterization laboratories (i.e. tertiary-care hospitals; THs) and nine without (i.e. secondary-care hospitals; SHs). Patients were assessed clinically at hospital discharge and after 3 and 12 months. RESULTS: In total, 1133 consecutive patients were recruited: 599 (52.9%) in THs and 534 (47.1%) in SHs. The use of specific class-I interventions (i.e. aspirin, clopidogrel, beta-blockers, angiotensin-converting enzyme inhibitors and statins) was more common in THs (P< .01) and more patients in THs underwent revascularization while in hospital (43% vs. 30%; P< .01). The number of SH patients who were readmitted for NSTEACS at 1 year was 5-fold greater than the number of TH patients (12.8% vs. 2.3%; P< .01), and hospital type was a predictor of an adverse event. CONCLUSIONS: Patients admitted for NSTEACS to a hospital without a catheterization laboratory were managed less invasively and their drug treatment was less likely to have been modified to match guideline recommendations. In addition to other well-known prognostic factors, hospital type can also have an influence on patient outcomes.

24-hour and nighttime blood pressures in type 2 diabetic hypertensive patients following morning or evening administration of olmesartan.

Ambulatory blood pressure monitoring (ABPM) allows determining of the nocturnal blood pressure fall (NBPF). An NBPF below 10% (nondipper pattern) has been related to increased cardiovascular risk, and it is a common finding in type 2 diabetic hypertensive patients. The authors evaluated the impact on 24-hour blood pressure, NBPF, and albuminuria of olmesartan 40 mg, administered in a morning- vs a nocturnal-based dosing scheme, in type 2 diabetic patients with newly diagnosed hypertension. Using a crossover design, 40 patients (42.1% men) received olmesartan 40 mg once daily at wake up or bedtime for 8 weeks. Patients underwent 24-hour ABPM at baseline and at weeks 8 and 16, and albumin to creatinine ratio was measured at baseline and 8 weeks. Night systolic blood pressure (BP) (P=.007) and mean BP (P=.012) were significantly reduced following the bedtime dose, compared with morning dosing. Night BP fall (%) was significantly reduced by bedtime dosing, compared with morning dosing (P=.0001). No differences were seen for urinary albumin excretion between both arms at week 8. Without affecting 24-hour BP control, night dosing of olmesartan increases nocturnal BP fall significantly more than conventional morning dosing, increasing the number of dipper diabetic hypertensive patients.