Myocardial fibrosis in arrhythmogenic cardiomyopathy: a genotype-phenotype correlation study.

AIMS: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is a life-threatening entity with a highly heterogeneous genetic background. Cardiac magnetic resonance (CMR) imaging can identify fibrofatty scar by late gadolinium enhancement (LGE). Our aim is to investigate genotype-phenotype correlation in ARVC/D mutation carriers, focusing on CMR-LGE and myocardial fibrosis patterns. METHODS AND RESULTS: A cohort of 44 genotyped patients, 33 with definite and 11 with borderline ARVC/D diagnosis, was characterized using CMR and divided into groups according to their genetic condition (desmosomal, non-desmosomal mutation, or negative). We collected information on cardiac volumes and function, as well as LGE pattern and extension. In addition, available ventricular myocardium samples from patients with pathogenic gene mutations were histopathologically analysed. Half of the patients were women, with a mean age of 41.6 ± 17.5 years. Next-generation sequencing identified a potential pathogenic mutation in 71.4% of the probands. The phenotype varied according to genetic status, with non-desmosomal male patients showing lower left ventricular (LV) systolic function. LV fibrosis was similar between groups, but distribution in non-desmosomal patients was frequently located at the posterolateral LV wall; a characteristic LV subepicardial circumferential LGE pattern was significantly associated with ARVC/D caused by desmin mutation. Histological analysis showed increased fibrillar connective tissue and intercellular space in all the samples. CONCLUSION: Desmosomal and non-desmosomal mutation carriers showed different morphofunctional features but similar LV LGE presence. DES mutation carriers can be identified by a specific and extensive LV subepicardial circumferential LGE pattern. Further studies should investigate the specificity of LGE in ARVC/D.

Diagnosis, management and mortality in acute aortic syndrome: results of the Spanish Registry of Acute Aortic Syndrome (RESA-II).

BACKGROUND: Recent advances in the diagnosis and treatment of acute aortic syndrome should improve the outcome of this disease. The Spanish Registry of Acute Aortic Syndrome aimed to assess current results in acute aortic syndrome management in a wide cohort of hospitals in the same geographical area. METHODS: From January 2012 to January 2014, 26 tertiary hospitals included 629 consecutive patients with acute aortic syndrome: 73% men, mean age 64.7±14 years (range 22-92), 443 type A (70.4%) and 186 type B (29.6%). RESULTS: Time elapsed between symptom onset and diagnosis was <12 hours in 70.7% of cases and <24 hours in 84.0% (median 5 hours; 25th-75th percentiles, 2.7-15.5 hours). Computed tomography was the first diagnostic technique in 78% of patients and transthoracic echocardiography in 15%. Surgical treatment was indicated in 78.3% of type A acute aortic syndrome. The interval between diagnosis and surgery was 4.8 hours (quartile 1-3, 2.5-11.4 hours). Among the patients with type B acute aortic syndrome, treatment was medical in 116 cases (62.4%), endovascular in 61 (32.8%) and surgical in nine (4.8%). Type A mortality during hospitalisation was 25.1% in patients treated surgically and 68% in those treated medically. Mortality in type B was 13.8% in those with medical treatment, 18.0% with endovascular therapy and 33.0% with surgical treatment. CONCLUSION: Improvements in the diagnosis and treatment of acute aortic syndrome have not resulted in a significant reduction in hospital mortality. The results of this study reflect more overall and less selected information on acute aortic syndrome management and the need for sustained advances in the therapeutic strategy of acute aortic syndrome.

Clinical and Genetic Diagnosis of Nonischemic Sudden Cardiac Death.

INTRODUCTION AND OBJECTIVES: Nonischemic sudden cardiac death (SCD) is predominantly caused by cardiomyopathies and channelopathies. There are many diagnostic tests, including some complex techniques. Our aim was to analyze the diagnostic yield of a systematic diagnostic protocol in a specialized unit. METHODS: The study included 56 families with at least 1 index case of SCD (resuscitated or not). Survivors were studied with electrocardiogram, advanced cardiac imaging, exercise testing, familial study, genetic testing and, in some cases, pharmacological testing. Families with deceased probands were studied using the postmortem findings, familial evaluation, and molecular autopsy with next-generation sequencing (NGS). RESULTS: A positive diagnosis was obtained in 80.4% of the cases, with no differences between survivors and nonsurvivors (P=.53). Cardiac channelopathies were more prevalent among survivors than nonsurvivors (66.6% vs 40%, P=.03). Among the 30 deceased probands, the definitive diagnosis was given by autopsy in 7. A diagnosis of cardiomyopathy tended to be associated with a higher event rate in the family. Genetic testing with NGS was performed in 42 index cases, with a positive result in 28 (66.6%), with no differences between survivors and nonsurvivors (P=.21). CONCLUSIONS: There is a strong likelihood of reaching a diagnosis in SCD after a rigorous protocol, with a more prevalent diagnosis of channelopathy among survivors and a worse familial prognosis in cardiomyopathies. Genetic testing with NGS is useful and its value is increasing with respect to the Sanger method.

[Left ventricular dysfunction induced by monomorphic ventricular arrhythmias: large improvement in ventricular function after radiofrequency ablation of the arrhythmic source]. / Disfunción ventricular izquierda inducida por arritmias ventriculares monomórficas: gran mejoría de la función ventricular tras ablación con radiofrecuencia del foco arrítmico.

Left ventricular systolic dysfunction related to ventricular arrhythmias is a relatively poorly understood entity. To increase our knowledge base, we describe 5 patients in whom the link between ventricular dysfunction and ventricular arrhythmia was unequivocally established. All patients had repetitive monomorphic ventricular arrhythmias and left ventricular systolic dysfunction (ejection fraction < or =40% and end-diastolic size > or =55 mm). The arrhythmogenic source was identified by electrophysiological study (right ventricle in 2 patients, left ventricle in 2, and left sinus of Valsalva in one), and was eliminated in all patients by radiofrequency catheter ablation. At 7+/-2 months post-ablation, large improvements were seen in left ventricular function and remodeling (ejection fraction >/=50% and end-diastolic size < or =51 mm in all cases), with no recurrence of arrhythmia during follow-up (10-69 months). This finding confirms that recurring ventricular arrhythmias can induce left ventricular dysfunction which may be reversible after ablation.

Utility of adenosine 5'-triphosphate in predicting early recurrence after successful ablation of manifest accessory pathways.

OBJECTIVES: The purpose of this study was to determine whether administration of adenosine 5'-triphosphate (ATP; 20-40 mg) after successful ablation of accessory pathway (AP) with manifest preexcitation is useful for detecting residual conduction and predicting early recurrences. BACKGROUND: The reported incidence of recurrence of AP conduction after an initially successful procedure is 5% to 10%. Little information on the variables related to early recurrence has been reported. METHODS: We prospectively used 108 ATP tests on 100 consecutive patients (66 men, mean age 36 +/- 15 years) with manifest preexcitation. Five minutes after successful ablation, intravenous boluses of ATP at increasing doses were injected until the target effect of second- or third-degree AV block or AP conduction was observed. RESULTS: The effect of ATP was AV block (negative test) in 82 cases (76%), conduction over previously ablated AP (positive test) in 9 cases (8.3%), and no achievement of target effect (nondiagnostic test) in 17 cases (15.7%). Thirteen early recurrences were observed in 12 patients. In all 9 (100%) patients with positive ATP test and in 4 (4.9%) of the 82 patients with negative ATP test, conduction over the AP recurred (relative risk 20; 95% confidence interval 8-53; P < .000001). The diagnostic accuracy of the test (analyzing the target effect) was 95%, sensitivity 69%, specificity 100%, and positive and negative predictive values 100% and 95%, respectively. CONCLUSIONS: ATP administration after successful ablation of APs has a high predictive value for early recurrence and may help optimize the duration of the ablation procedure.

[Does the EuroSCORE identify patients at minimum risk of mortality from heart surgery?]. / ¿Se puede identificar mediante el EuroSCORE a los pacientes con mortalidad mínima en cirugía cardíaca?

INTRODUCTION AND OBJECTIVES: Risk of hospital death is one of the key factors considered by the clinical cardiologist when weighting indications for surgery. Risk estimation scales establish distinct levels of risk in quantitative terms. The aim of the present study was to investigate whether a low EuroSCORE value corresponds to low mortality in our setting. PATIENTS AND METHODS: During 1999-2000 we prospectively calculated the EuroSCORE for all patients who underwent isolated coronary (CS) or valvular (VS) surgery. We then analyzed intrahospital mortality of patients with a low EuroSCORE. The validation group consisted of patients who underwent surgery in 2001 and obtained a low EuroSCORE. RESULTS: During 1999-2000 we identified 116 patients (16.2% of all patients treated with isolated CS or CV) with a low EuroSCORE (50 8.6 years; 65% male). Fifty-seven of these patients underwent isolated CS, and 59 of them isolated VS. Intrahospital mortality was zero. In 2001 we identified 59 (16.1%) such patients (49 8.7 years; 68% male), of whom 35 underwent isolated CS and 24 underwent isolated VS. Intrahospital mortality during this period was again zero. CONCLUSIONS: A low EuroSCORE identifies a population of patients with minimum risk of mortality after isolated coronary or valve surgery. The score may be useful as a sentinel indicator in analyses of the complex issue of quality of cardiac surgery.