Clinical Risk Score to Predict Pathogenic Genotypes in Patients With Dilated Cardiomyopathy.

BACKGROUND: Although genotyping allows family screening and influences risk-stratification in patients with nonischemic dilated cardiomyopathy (DCM) or isolated left ventricular systolic dysfunction (LVSD), its result is negative in a significant number of patients, limiting its widespread adoption. OBJECTIVES: This study sought to develop and externally validate a score that predicts the probability for a positive genetic test result (G+) in DCM/LVSD. METHODS: Clinical, electrocardiogram, and echocardiographic variables were collected in 1,015 genotyped patients from Spain with DCM/LVSD. Multivariable logistic regression analysis was used to identify variables independently predicting G+, which were summed to create the Madrid Genotype Score. The external validation sample comprised 1,097 genotyped patients from the Maastricht and Trieste registries. RESULTS: A G+ result was found in 377 (37%) and 289 (26%) patients from the derivation and validation cohorts, respectively. Independent predictors of a G+ result in the derivation cohort were: family history of DCM (OR: 2.29; 95% CI: 1.73-3.04; P < 0.001), low electrocardiogram voltage in peripheral leads (OR: 3.61; 95% CI: 2.38-5.49; P < 0.001), skeletal myopathy (OR: 3.42; 95% CI: 1.60-7.31; P = 0.001), absence of hypertension (OR: 2.28; 95% CI: 1.67-3.13; P < 0.001), and absence of left bundle branch block (OR: 3.58; 95% CI: 2.57-5.01; P < 0.001). A score containing these factors predicted a G+ result, ranging from 3% when all predictors were absent to 79% when ≥4 predictors were present. Internal validation provided a C-statistic of 0.74 (95% CI: 0.71-0.77) and a calibration slope of 0.94 (95% CI: 0.80-1.10). The C-statistic in the external validation cohort was 0.74 (95% CI: 0.71-0.78). CONCLUSIONS: The Madrid Genotype Score is an accurate tool to predict a G+ result in DCM/LVSD.

Association of Genetic Variants With Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.

BACKGROUND: The clinical relevance of genetic variants in nonischemic dilated cardiomyopathy (DCM) is unsettled. OBJECTIVES: The study sought to assess the prognostic impact of disease-causing genetic variants in DCM. METHODS: Baseline and longitudinal clinical data from 1,005 genotyped DCM probands were retrospectively collected at 20 centers. A total of 372 (37%) patients had pathogenic or likely pathogenic variants (genotype positive) and 633 (63%) were genotype negative. The primary endpoint was a composite of major adverse cardiovascular events. Secondary endpoints were end-stage heart failure (ESHF), malignant ventricular arrhythmia (MVA), and left ventricular reverse remodeling (LVRR). RESULTS: After a median follow-up of 4.04 years (interquartile range: 1.70-7.50 years), the primary endpoint had occurred in 118 (31.7%) patients in the genotype-positive group and in 125 (19.8%) patients in the genotype-negative group (hazard ratio [HR]: 1.51; 95% confidence interval [CI]: 1.17-1.94; P = 0.001). ESHF occurred in 60 (16.1%) genotype-positive patients and in 55 (8.7%) genotype-negative patients (HR: 1.67; 95% CI: 1.16-2.41; P = 0.006). MVA occurred in 73 (19.6%) genotype-positive patients and in 77 (12.2%) genotype-negative patients (HR: 1.50; 95% CI: 1.09-2.07; P = 0.013). LVRR occurred in 39.6% in the genotype-positive group and in 46.2% in the genotype-negative group (P = 0.047). Among individuals with baseline left ventricular ejection fraction ≤35%, genotype-positive patients exhibited more major adverse cardiovascular events, ESHF, and MVA than their genotype-negative peers (all P < 0.02). LVRR and clinical outcomes varied depending on the underlying affected gene. CONCLUSIONS: In this study, DCM patients with pathogenic or likely pathogenic variants had worse prognosis than genotype-negative individuals. Clinical course differed depending on the underlying affected gene.

Amiloidosis cardiaca por transtiretina: la gammagrafía mostró el camino / Transthyretin amyloidosis: Scintigraphy showing the way

Fundamento y objetivo: La amiloidosis cardiaca es una enfermedad grave producida por el depósito extracelular a nivel cardiaco de diversas sustancias que se identifican con el análisis de una biopsia endomiocárdica, técnica invasiva, poco accesible y de difícil interpretación. Debido a que las diversas entidades suponen diferente evolución, tratamiento y pronóstico, tiene gran relevancia clínica conocer el subtipo de esta patología. El objetivo es presentar diferentes técnicas diagnósticas no invasivas que nos puedan orientar a sospechar la amiloidosis por transtiretina. Método: Con este caso clínico reflejamos tanto la dificultad para llegar al diagnóstico del subtipo de amiloidosis como la utilidad de las pruebas radiológicas, la gammagrafía y la cardiorresonancia, en el diagnóstico diferencial de amiloidosis cardiaca. Resultados: El intenso depósito cardiaco de forma biventricular en la gammagrafía cardiaca con 99mTc-DPD como el realce tardío biventricular circunferencial en la cardiorresonancia son herramientas muy útiles para orientar hacia el diagnóstico de la amiloidosis por transtiretina.

Background and objetive: Cardiac amyloidosis is a very severe disease caused by extracellular deposition of insoluble fibrils. The gold standard for diagnosing cardiac amyloidosis is an endomyocardial biopsy. This technique is invasive, limited to experienced centers, and thus not widely available. It is required to perform special techniques to precisely determine the amyloid type as the treatment, evolution and prognosis of the disease differs greatly according the type of amyloid present. Method: In this case report we want to present the difficulties for diagnosing the types of amyloid involved in cardiac amyloidosis as well as the usefulness of cardiac MRI for diagnosing cardiac amyloidosis, particularly when performed with the use of the gadolinium as an imaging agent. Results: Biventricular, concentric late gadolinium enhancement on cardiac magnetic resonance and on technetium pyrophosphate scan (99mTc-DPD) showed to be helpful in the diagnosis of senile cardiac amyloidosis transthyrenin variant.