Role of TBX20 Truncating Variants in Dilated Cardiomyopathy and Left Ventricular Noncompaction.

BACKGROUND: Less than 40% of patients with dilated cardiomyopathy (DCM) have a pathogenic/likely pathogenic genetic variant identified. TBX20 has been linked to congenital heart defects; although an association with left ventricular noncompaction (LVNC) and DCM has been proposed, it is still considered a gene with limited evidence for these phenotypes. This study sought to investigate the association between the TBX20 truncating variant (TBX20tv) and DCM/LVNC. METHODS: TBX20 was sequenced by next-generation sequencing in 7463 unrelated probands with a diagnosis of DCM or LVNC, 22 773 probands of an internal comparison group (hypertrophic cardiomyopathy, channelopathies, or aortic diseases), and 124 098 external controls (individuals from the gnomAD database). Enrichment of TBX20tv in DCM/LVNC was calculated, cosegregation was determined in selected families, and clinical characteristics and outcomes were analyzed in carriers. RESULTS: TBX20tv was enriched in DCM/LVNC (24/7463; 0.32%) compared with internal (1/22 773; 0.004%) and external comparison groups (4/124 098; 0.003%), with odds ratios of 73.23 (95% CI, 9.90-541.45; P<0.0001) and 99.76 (95% CI, 34.60-287.62; P<0.0001), respectively. TBX20tv was cosegregated with DCM/LVNC phenotype in 21 families for a combined logarythm of the odds score of 4.53 (strong linkage). Among 57 individuals with TBX20tv (49.1% men; mean age, 35.9±20.8 years), 41 (71.9%) exhibited DCM/LVNC, of whom 14 (34.1%) had also congenital heart defects. After a median follow-up of 6.9 (95% CI, 25-75:3.6-14.5) years, 9.7% of patients with DCM/LVNC had end-stage heart failure events and 4.8% experienced malignant ventricular arrhythmias. CONCLUSIONS: TBX20tv is associated with DCM/LVNC; congenital heart defect is also present in around one-third of cases. TBX20tv-associated DCM/LVNC is characterized by a nonaggressive phenotype, with a low incidence of major cardiovascular events. TBX20 should be considered a definitive gene for DCM and LVNC and routinely included in genetic testing panels for these phenotypes.

Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure.

BACKGROUND: There is scarce evidence supporting the clinical utility of congestive intrarenal venous flow (IRVF) patterns in patients with acute heart failure. OBJECTIVES: This study aims to: 1) investigate the association between IRVF patterns and the odds of worsening renal function (WRF); 2) track the longitudinal changes of serum creatinine (sCr) across IRVF at predetermined points and its association with decongestion; and 3) explore the relationship between IRVF/WRF categories and patient outcomes. METHODS: IRVF was assessed at baseline (pre-decongestive therapy), 72 hours, and 30 and 90 days postdischarge. Changes in sCr trajectories across dynamic IRVF variations and parameters of decongestion were assessed using linear mixed effect models. The association between IRVF/WRF categories and outcomes was evaluated using univariable/multivariable models. RESULTS: In this prospective, multicenter study with 188 participants, discontinuous IRVF patterns indicated higher odds of WRF (OR: 3.90 [95% CI: 1.24-12.20]; P = 0.020 at 72 hours; and OR: 5.76 [95% CI: 1.67-19.86]; P = 0.006 at 30 days) and an increase in sCr (Δ-72 hours 0.14 mg/dL [95% CI: 0.06-0.22]; P = 0.001; Δ-discharge 0.13 mg/dL [95% CI: 0.03-0.23]; P = 0.007). However, the diuretic response and decongestion significantly influenced the magnitude of these changes. Patients exhibiting both WRF and discontinuous IRVF at 30 days experienced an increased hazard of adverse events (HR: 5.96 [95% CI: 2.63-13.52]; P < 0.001). CONCLUSIONS: Discontinuous IRVF identifies patients with higher odds of WRF during admission and postdischarge periods. Nonetheless, adequate diuretic response and decongestion could modify this association. Patients showing both WRF and discontinuous IRVF at 30 days had increased rates of adverse events.

Estimation of the QTc interval in the presence of right bundle branch block: A comparative study using validated formulae for left bundle branch block.

BACKGROUND: Adequate measurement of the QT interval is of clinical importance in order to identify patients at higher risk for ventricular arrhythmias. Previous studies have described different methods to estimate baseline QT in patients with left bundle branch block (LBBB). However, the evidence regarding the assessment of the QT in patients with right bundle branch block (RBBB) is scarce. AIM: To analyze the feasibility and reliability of the different formulae described for LBBB in the estimation of the baseline QT in the presence of RBBB. METHODS: We performed an observational study including patients who underwent electrophysiology study and/or ablation. Two types of RBBB were considered: 1) pacing-induced and 2) transient true RBBB. QRS, JT and QT intervals were measured during baseline and RBBB. Estimated QTc was calculated using LBBB formulae: Bogossian, Rautaharju, Tabatabaei, Tang-Rabkin, Yankelson, Wang. Linear correlation and intraclass correlation coefficients (ICC) were used to assess the reliability of these formulae for the estimation of baseline QTc. RESULTS: We finally included a total of 100 patients. Correlations between baseline and estimated QTc were strong (R > 0.7) for all the formulae except for Tabatabaei. Yankelson and Wang showed the highest reliability (ICC = 0.775 and 0.727, respectively). Yankelson appeared to be the most accurate formula, with a mean estimated QTc closest to baseline values. CONCLUSION: Previously described formulae for LBBB exhibited marked differences regarding reliability in the estimation of the QTc interval in the presence of RBBB. According to our results, Yankelson showed the most consistent and accurate agreement in this setting.

Role of Early Assesment of Diuresis and Natriuresis in Detecting In-Hospital Diuretic Resistance in Acute Heart Failure.

Background and Purpose: European Guidelines recommend early evaluation of diuresis and natriuresis after the first administration of diuretic to identify patients with insufficient diuretic response during acute heart failure. The aim of this work is to evaluate the prevalence and characteristics of patients with insufficient diuretic response according to this new algorithm. Methods: Prospective observational single centre study of consecutive patients with acute heart failure and congestive signs. Clinical evaluation, echocardiography and blood tests were performed. Diuretic naïve patients received 40 mg of intravenous furosemide. Patients on an oupatient diuretic regimen received 2 times the ambulatory dose. The diuresis volume was assessed 6 h after the first loop diuretic administration, and a spot urinary sample was taken after 2 h. Insufficient diuretic response was defined as natriuresis <70 mEq/L or diuresis volume <600 ml. Results: From January 2020 to December 2021, 73 patients were included (59% males, median age 76 years). Of these, 21 patients (28.8%, 95%CI 18.4; 39.2) had an insufficient diuretic response. Diuresis volume was <600 ml in 13 patients (18.1%), and 12 patients (16.4%) had urinary sodium <70 mEq/L. These patients had lower systolic blood pressure, worse glomerular filtration rate, and higher aldosterone levels. Ambulatory furosemide dose was also higher. These patients required more frequently thiazides and inotropes during admission. Conclusion: The diagnostic algorithm based on diuresis and natriuresis was able to detect up to 29% of patients with insufficient diuretic response, who showed some characteristics of more advanced disease.

Infective endocarditis in children and adolescents: a different profile with clinical implications.

BACKGROUND: Our aim was to compare pediatric infective endocarditis (IE) with the clinical profile and outcomes of IE in adults. METHODS: Prospective multicenter registry in 31 Spanish hospitals including all patients with a diagnosis of IE from 2008 to 2020. RESULTS: A total of 5590 patients were included, 49 were <18 years (0.1%). Congenital heart disease (CHD) was present in 31 children and adolescents (63.2%). Right-sided location was more common in children/adolescents than in adults (46.9% vs. 6.3%, P < 0.001). Pediatric pulmonary IE was more frequent in patients with CHD (48.4%) than in those without (5.6%), P = 0.004. Staphylococcus aureus etiology tended to be more common in pediatric patients (32.7%) than in adults (22.3%), P = 0.082. Heart failure was less common in pediatric patients than in adults, due to the lower rate of heart failure in children/adolescents with CHD (9.6%) with respect to those without CHD (44.4%), P = 0.005. Inhospital mortality was high in both children, and adolescents and adults (16.3% vs. 25.9%; P = 0.126). CONCLUSIONS: Most IE cases in children and adolescents are seen in patients with CHD that have a more common right-sided location and a lower prevalence of heart failure than patients without CHD. IE in children and adolescents without CHD has a more similar profile to IE in adults. IMPACT: Infective endocarditis (IE) in children and adolescents is often seen in patients with congenital heart disease (CHD). Right-sided location is the most common in patients with CHD and heart failure is less common as a complication compared with patients without CHD. Infective endocarditis (IE) in children/adolescents without CHD has a more similar profile to IE in adults. In children/adolescents without CHD, locations were similar to adults, including a predominance of left-sided IE. Acute heart failure was the most frequent complication, seen mainly in adults, and in children/adolescents without CHD.

Non-HACEK gram negative bacilli endocarditis: Analysis of a national prospective cohort.

BACKGROUND: Infective endocarditis (IE) due to non-HACEK bacilli (Haemophilus species, Actinobacillus, Cardiobacterium, Eikenella, or Kingella) is uncommon and poorly described. The objectives of this study were to describe non-HACEK Gram-Negative Bacilli (GNB) IE cases and compare characteristic of IE produced by Enterobacterales and non-fermenting (NF) GNB. METHODS: From January 2008 to December 2018, 3910 consecutive patients with definitive IE diagnosis, defined with Modified Duke criteria, either clinical or pathological criteria (e.g. demonstration of non-HACEK GNB in valve culture)were prospectively included. RESULTS: A total of 104 IE cases were caused by non-HACEK GNB (2.6%). Compared to IE due to other microorganisms (excluding HACEK GNB), patients with non-HACEK GNB IE presented with higher age (71 years [IQR 62-78] vs 68 years [IQR: 57-77]; p = 0.026), higher proportion of women (52% vs 31.5%, p < 0.001), higher Charlson Index (5 [IQR: 4-8] vs 4 [IQR 3-7], p = 0.003) and higher in-hospital mortality (36.5% vs 27.1%, p = 0.034). Enterobacterales cases were more frequently associated with genitourinary focus (32.8% vs 5.0%, p = 0.001). NFGNB endocarditis more frequently affected right valves (20.0% vs. 6.3%, p = 0.033), had more common healthcare-related acquisition (67.5% vs. 43.7%, p = 0.030) and venous catheter as focus (40.0% vs. 17.2%, p = 0.019). In the multivariant model, factors related with hospital mortality were: age (OR 1.05, 95%CI 1.00-1.09, p = 0.042), prosthetic valve (OR 2.31, 95%CI 0.90-5.88, p = 0.080), and not performing surgery when indicated (OR 3.60, 95%CI 1.17-11.05, p = 0.025).Patients treated with quinolone combination had lower mortality (OR 0.29; 95%CI 0.09-0.96; p = 0.043). CONCLUSION: Non-HACEK GNB IE is a rare infection characterized by affecting elderly patients with high comorbidity, nosocomial acquisition and unfavorable outcome. Age, prosthetic valve and not performing surgery when indicated are associated with mortality.