Penetrance of Dilated Cardiomyopathy in Genotype-Positive Relatives.

BACKGROUND: Disease penetrance in genotype-positive (G+) relatives of families with dilated cardiomyopathy (DCM) and the characteristics associated with DCM onset in these individuals are unknown. OBJECTIVES: This study sought to determine the penetrance of new DCM diagnosis in G+ relatives and to identify factors associated with DCM development. METHODS: The authors evaluated 779 G+ patients (age 35.8 ± 17.3 years; 459 [59%] females; 367 [47%] with variants in TTN) without DCM followed at 25 Spanish centers. RESULTS: After a median follow-up of 37.1 months (Q1-Q3: 16.3-63.8 months), 85 individuals (10.9%) developed DCM (incidence rate of 2.9 per 100 person-years; 95% CI: 2.3-3.5 per 100 person-years). DCM penetrance and age at DCM onset was different according to underlying gene group (log-rank P = 0.015 and P <0.01, respectively). In a multivariable model excluding CMR parameters, independent predictors of DCM development were: older age (HR per 1-year increase: 1.02; 95% CI: 1.0-1.04), an abnormal electrocardiogram (HR: 2.13; 95% CI: 1.38-3.29); presence of variants in motor sarcomeric genes (HR: 1.92; 95% CI: 1.05-3.50); lower left ventricular ejection fraction (HR per 1% increase: 0.86; 95% CI: 0.82-0.90) and larger left ventricular end-diastolic diameter (HR per 1-mm increase: 1.10; 95% CI: 1.06-1.13). Multivariable analysis in individuals with cardiac magnetic resonance and late gadolinium enhancement assessment (n = 360, 45%) identified late gadolinium enhancement as an additional independent predictor of DCM development (HR: 2.52; 95% CI: 1.43-4.45). CONCLUSIONS: Following a first negative screening, approximately 11% of G+ relatives developed DCM during a median follow-up of 3 years. Older age, an abnormal electrocardiogram, lower left ventricular ejection fraction, increased left ventricular end-diastolic diameter, motor sarcomeric genetic variants, and late gadolinium enhancement are associated with a higher risk of developing DCM.

Risks of Ventricular Arrhythmia and Heart Failure in Carriers of RBM20 Variants.

BACKGROUND: Variants in RBM20 are reported in 2% to 6% of familial cases of dilated cardiomyopathy and may be associated with fatal ventricular arrhythmia and rapid heart failure progression. We sought to determine the risk of adverse events in RBM20 variant carriers and the impact of sex on outcomes. METHODS: Consecutive probands and relatives carrying RBM20 variants were retrospectively recruited from 12 cardiomyopathy units. The primary end point was a composite of malignant ventricular arrhythmia (MVA) and end-stage heart failure (ESHF). MVA and ESHF end points were also analyzed separately and men and women compared. Left ventricular ejection fraction (LVEF) contemporary to MVA was examined. RBM20 variant carriers with left ventricular systolic dysfunction (RBM20LVSD) were compared with variant-elusive patients with idiopathic left ventricular systolic dysfunction. RESULTS: Longitudinal follow-up data were available for 143 RBM20 variant carriers (71 men; median age, 35.5 years); 7 of 143 had an MVA event at baseline. Thirty of 136 without baseline MVA (22.0%) reached the primary end point, and 16 of 136 (11.8%) had new MVA with no significant difference between men and women (log-rank P=0.07 and P=0.98, respectively). Twenty of 143 (14.0%) developed ESHF (17 men and 3 women; log-rank P<0.001). Four of 10 variant carriers with available LVEF contemporary to MVA had an LVEF >35%. At 5 years, 15 of 67 (22.4%) RBM20LVSD versus 7 of 197 (3.6%) patients with idiopathic left ventricular systolic dysfunction had reached the primary end point (log-rank P<0.001). RBM20 variant carriage conferred a 6.0-fold increase in risk of the primary end point. CONCLUSIONS: RBM20 variants are associated with a high risk of MVA and ESHF compared with idiopathic left ventricular systolic dysfunction. The risk of MVA in male and female RBM20 variant carriers is similar, but male sex is strongly associated with ESHF.

Development and Validation of a Prediction Model and Score for Transthyretin Cardiac Amyloidosis Diagnosis: T-Amylo.

BACKGROUND: Although transthyretin cardiac amyloidosis (ATTR-CA) is often underdiagnosed, clinical suspicion is essential for early diagnosis. OBJECTIVES: The aim of this study was to develop and validate a feasible prediction model and score to facilitate the diagnosis of ATTR-CA. METHODS: This retrospective multicenter study enrolled consecutive patients who underwent 99mTc-DPD scintigraphy for suspected ATTR-CA. ATTR-CA was diagnosed if Grade 2 or 3 cardiac uptake was evidenced on 99mTc-DPD scintigraphy in the absence of a detectable monoclonal component or by demonstration of amyloid by biopsy. A prediction model for ATTR-CA diagnosis was developed in a derivation sample of 227 patients from 2 centers using multivariable logistic regression with clinical, electrocardiography, analytical, and transthoracic echocardiography variables. A simplified score was also created. Both of them were validated in an external cohort (n = 895) from 11 centers. RESULTS: The obtained prediction model combined age, gender, carpal tunnel syndrome, interventricular septum in diastole thickness, and low QRS interval voltages, with an area under the curve (AUC) of 0.92. The score had an AUC of 0.86. Both the T-Amylo prediction model and the score showed a good performance in the validation sample (ie, AUC: 0.84 and 0.82, respectively). They were tested in 3 clinical scenarios of the validation cohort: 1) hypertensive cardiomyopathy (n = 327); 2) severe aortic stenosis (n = 105); and 3) heart failure with preserved ejection fraction (n = 604), all with good diagnostic accuracy. CONCLUSIONS: The T-Amylo is a simple prediction model that improves the prediction of ATTR-CA diagnosis in patients with suspected ATTR-CA.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Differences between patient-driven adherence to vitamin K antagonists and direct oral anticoagulants. Do few missed doses matter? ACO-MEMS Study.

INTRODUCTION: Lack of INR controls might affect the adherence to direct oral anticoagulants (DOAC). The vast majority of studies that addresses adherence to anticoagulants are retrospective and based on pharmacy refill data. Our aim was to compare the adherence between vitamin K antagonists (VKA) and DOAC and to analyze the clinical relevance of non-adherence. MATERIALS AND METHODS: A prospective two-arm observational cohort study was performed in two Spanish public hospitals. Adherence was assessed by Medication Event Monitoring System. Relationship between adherence and events during follow-up and time in therapeutic range (TTR) in the VKA group were analyzed. RESULTS: 257 patients were included (132 DOAC and 125 VKA). Monitoring time was 120 days (101-133). Patients in VKA group showed higher taking adherence (97.9% vs. 95.8%) and less non-adherent patients of >5% and >10% of the doses, without differences in >20% of the doses. Taking adherence was strongly associated with TTR (AUC: 0.89, CI 95%: 0.81-0.97 of TTR for detection of non-adherent patients of >10% of doses). During a follow-up of 1.8 years (1.6-2) non-adherent patients of >5% of doses presented more thromboembolic events (HR 6.1, CI95% 1.3-28.1). CONCLUSIONS: Although adherence to oral anticoagulant therapy was excellent, it was higher to VKA than to DOAC. Time in therapeutic range was highly sensitive to few missed doses of AVK. Non-adherence of >5% of prescribed doses had high clinical relevance.

[Prognostic impact of interventional approach in non-ST segment elevation acute coronary syndrome in very elderly patients]. / Impacto pronóstico del abordaje intervencionista en el paciente muy anciano con síndrome coronario agudo sin elevación del segmento ST.

INTRODUCTION AND OBJECTIVES: In moderate or high risk non-ST segment elevation acute coronary syndrome, clinical practice guidelines recommend a coronary angiography with intent to revascularize. However, evidence to support this recommendation in very elderly patients is poor. METHODS: All patients over 85 years old admitted to our hospital between 2004 and 2009 with a diagnosis of non-ST segment elevation acute coronary syndrome were retrospectively included. Using a propensity score, patients undergoing the interventional approach and those undergoing conservative management were matched and compared for survival and survival without ischemic events. RESULTS: We included 228 consecutive patients with a mean age of 88 years (range: 85 to 101). Those in the interventional approach group (n=100) were younger, with a higher proportion of males and less comorbidity, less cognitive impairment and lower troponin I levels compared with patients in the conservative management group (n=128). We matched 63 patients from the interventional approach group and 63 from the conservative management group using propensity score. In the matched patients, the interventional approach group exhibited better survival (log rank 4.24; P=.039) and better survival free of ischemic events (log rank 8.63; P=.003) at the 3-year follow-up. In the whole population, adjusted for propensity score quintiles, the interventional approach group had lower mortality (hazard ratio 0.52; 95% confidence interval: 0.32-0.85) and a better survival free of ischemic events (hazard ratio 0.48; 95% confidence interval: 0.32-0.74). CONCLUSIONS: Nearly all the very elderly patients admitted with non-ST segment elevation acute coronary syndrome were of moderate or high risk. In these patients, the interventional approach was associated with overall better survival and better survival free of ischemic events.