Differential clinical characteristics and prognosis of intraventricular conduction defects in patients with chronic heart failure

Intraventricular conduction defects (IVCDs) can impair prognosis of heart failure (HF), but their specific impact is not well established. This study aimed to analyse the clinical profile and outcomes of HF patients with LBBB, right bundle branch block (RBBB), left anterior fascicular block (LAFB), and no IVCDs. Clinical variables and outcomes after a median follow-up of 21 months were analysed in 1762 patients with chronic HF and LBBB (n = 532), RBBB (n = 134), LAFB (n = 154), and no IVCDs (n = 942). LBBB was associated with more marked LV dilation, depressed LVEF, and mitral valve regurgitation. Patients with RBBB presented overt signs of congestive HF and depressed right ventricular motion. The LAFB group presented intermediate clinical characteristics, and patients with no IVCDs were more often women with less enlarged left ventricles and less depressed LVEF. Death occurred in 332 patients (interannual mortality = 10.8%): cardiovascular in 257, extravascular in 61, and of unknown origin in 14 patients. Cardiac death occurred in 230 (pump failure in 171 and sudden death in 59). An adjusted Cox model showed higher risk of cardiac death and pump failure death in the LBBB and RBBB than in the LAFB and the no IVCD groups. LBBB and RBBB are associated with different clinical profiles and both are independent predictors of increased risk of cardiac death in patients with HF. A more favourable prognosis was observed in patients with LAFB and in those free of IVCDs. Further research in HF patients with RBBB is warranted

Assessment of two complementary influenza surveillance systems : Sentinel primary care influenza-like illness versus severe hospitalized laboratory-confirmed influenza using the moving epidemic method

Monitoring seasonal influenza epidemics is the corner stone to epidemiological surveillance of acute respiratory virus infections worldwide. This work aims to compare two sentinel surveillance systems within the Daily Acute Respiratory Infection Information System of Catalonia (PIDIRAC), the primary care ILI and Influenza confirmed samples from primary care (PIDIRAC-ILI and PIDIRAC-FLU) and the severe hospitalized laboratory confirmed influenza system (SHLCI), in regard to how they behave in the forecasting of epidemic onset and severity allowing for healthcare preparedness. Epidemiological study carried out during seven influenza seasons (2010-2017) in Catalonia, with data from influenza sentinel surveillance of primary care physicians reporting ILI along with laboratory confirmation of influenza from systematic sampling of ILI cases and 12 hospitals that provided data on severe hospitalized cases with laboratory-confirmed influenza (SHLCI-FLU). Epidemic thresholds for ILI and SHLCI-FLU (overall) as well as influenza A (SHLCI-FLUA) and influenza B (SHLCI-FLUB) incidence rates were assessed by the Moving Epidemics Method. Epidemic thresholds for primary care sentinel surveillance influenza-like illness (PIDIRAC-ILI) incidence rates ranged from 83.65 to 503.92 per 100.000 h. Paired incidence rate curves for SHLCI-FLU/PIDIRAC-ILI and SHLCI-FLUA/PIDIRAC-FLUA showed best correlation index' (0.805 and 0.724 respectively). Assessing delay in reaching epidemic level, PIDIRAC-ILI source forecasts an average of 1.6 weeks before the rest of sources paired. Differences are higher when SHLCI cases are paired to PIDIRAC-ILI and PIDIRAC-FLUB although statistical significance was observed only for SHLCI-FLU/PIDIRAC-ILI (p-value Wilcoxon test = 0.039). The combined ILI and confirmed influenza from primary care along with the severe hospitalized laboratory confirmed influenza data from PIDIRAC sentinel surveillance system provides timely and accurate syndromic and virological surveillance of influenza from the community level to hospitalization of severe cases

Genetic Etiology for Alcohol-Induced Cardiac Toxicity

10.1016/j.jacc.2018.03.462Journal of the American College of Cardiology71202293-2302JACC

Natural History of MYH7-Related Dilated Cardiomyopathy.

Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 ± 19.2 years) recruited from 29 international centers. At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% ± 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of ≤35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare.This study has been funded by Instituto de Salud Carlos III (ISCIII) through the projects PI18/0004, PI20/0320, and PT17/0015/0043 (cofunded by European Regional Development Fund/European Social Fund “A way to make Europe”/“Investing in your future”). The Centro Nacional de Investigaciones Cardiovasculares (CNIC) is supported by the ISCIII, MCIN, the Pro-CNIC Foundation, and the Severo Ochoa Centers of Excellence program (CEX2020-001041-S). The Hospital Universitario Puerta de Hierro, the Hospital Sant Joan de Déu, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare and Low Prevalence Complex Diseases of the Heart. Dr de Frutos receives grant support from ISCIII (CM20/00101). Genetic examinations of Polish patients were funded with DETECTIN-HF grant from the ERA-CVD framework, NCBiR. Dr Baas has received funding from CVON2020B005 DOUBLEDOSE, Dutch Heart Foundation (Dekker 2015T041). Dr Fatkin has received funding from Victor Chang Cardiac Research Institute and NSW Health. Dr Lopes is funded by an MRC UK Clinical Academic Research Partnership award (MR/T005181/1). Dr Meder has received funding from the Deutsches Zentrum für Herz-Kreislauf-Forschung (German Center for Cardiovascular Research) and Informatics for Life (Klaus Tschira Foundation). Dr Kubanek has received grant support from the Ministry of Health, Czech Republic (NV19-08-00122) and IPO (Institute for Clinical and Experimental Medicine–IKEM, IN 00023001). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.S

Genetic landscape of 6089 inherited retinal dystrophies affected cases in Spain and their therapeutic and extended epidemiological implications

Inherited retinal diseases (IRDs), defined by dysfunction or progressive loss of photoreceptors, are disorders characterized by elevated heterogeneity, both at the clinical and genetic levels. Our main goal was to address the genetic landscape of IRD in the largest cohort of Spanish patients reported to date. A retrospective hospital-based cross-sectional study was carried out on 6089 IRD affected individuals (from 4403 unrelated families), referred for genetic testing from all the Spanish autonomous communities. Clinical, demographic and familiar data were collected from each patient, including family pedigree, age of appearance of visual symptoms, presence of any systemic findings and geographical origin. Genetic studies were performed to the 3951 families with available DNA using different molecular techniques. Overall, 53.2% (2100/3951) of the studied families were genetically characterized, and 1549 different likely causative variants in 142 genes were identified. The most common phenotype encountered is retinitis pigmentosa (RP) (55.6% of families, 2447/4403). The most recurrently mutated genes were PRPH2, ABCA4 and RS1 in autosomal dominant (AD), autosomal recessive (AR) and X-linked (XL) NON-RP cases, respectively; RHO, USH2A and RPGR in AD, AR and XL for non-syndromic RP; and USH2A and MYO7A in syndromic IRD. Pathogenic variants c.3386G > T (p.Arg1129Leu) in ABCA4 and c.2276G > T (p.Cys759Phe) in USH2A were the most frequent variants identified. Our study provides the general landscape for IRD in Spain, reporting the largest cohort ever presented. Our results have important implications for genetic diagnosis, counselling and new therapeutic strategies to both the Spanish population and other related populations

NT-proBNP Response to Sacubitril/Valsartan in Hospitalized Heart Failure Patients With Reduced Ejection Fraction: TRANSITION Study

Objectives: This study examined the effects of sacubitril/valsartan on N-terminal pro\u2013B-type natriuretic peptide (NT-proBNP) levels and determined patient characteristics associated with favorable NT-proBNP reduction response. Background: NT-proBNP levels reflect cardiac wall stress and predict event risk in patients with acute decompensated heart failure (ADHF). Methods: Post-hoc analysis of the TRANSITION (Comparison of Pre- and Post-discharge Initiation of Sacubitril/Valsartan Therapy in HFrEF Patients After an Acute Decompensation Event) study, including stabilized ADHF patients with reduced ejection fraction, randomized to open-label sacubitril/valsartan initiation in-hospital (pre-discharge) versus post-discharge. NT-proBNP was measured at randomization (baseline), discharge, and 4 and 10 weeks post-randomization. A favorable NT-proBNP response was defined as reduction to 641,000 pg/ml or &gt;30% from baseline. Results: In patients receiving sacubitril/valsartan in-hospital, NT-proBNP was reduced by 28% at discharge, with 46% of patients obtaining favorable NT-proBNP reduction response compared with a 4% reduction and 18% favorable response rate in patients initiated post-discharge (p &lt; 0.001). NT-proBNP was reduced similarly in patients initiating sacubitril/valsartan pre- and post-discharge (reduction at 4 weeks: 25%/22%; 10 weeks: 38%/34%) with comparable favorable response rates (46%/42% and 51%/48% at 4 and 10 weeks, respectively). NT-proBNP favorable response at 4 weeks was associated with lower risk of first heart failure (HF) rehospitalization or cardiovascular death through 26 weeks (hazard ratio: 0.57; 95% confidence interval [CI]: 0.38 to 0.86; p = 0.007). Predictors of a favorable response at 4 weeks were starting dose 6549/51 mg twice daily, higher baseline NT-proBNP, lower baseline serum creatinine, de novo HF, no atrial fibrillation, angiotensin-converting enzyme inhibitor\u2013naive or angiotensin receptor blocker\u2013naive, and no prior myocardial infarction. Conclusions: In-hospital initiation of sacubitril/valsartan produced rapid reductions in NT-proBNP, statistically significant at discharge. A favorable NT-proBNP response over time was associated with a better prognosis and predicted by higher starting dose and predisposing clinical profile. (Comparison of Pre- and Post-discharge Initiation of LCZ696 Therapy in HFrEF Patients After an Acute Decompensation Event [TRANSITION]; NCT02661217

Performance of Prognostic Risk Scores in Chronic Heart Failure Patients Enrolled in the European Society of Cardiology Heart Failure Long-Term Registry

Objectives: This study compared the performance of major heart failure (HF) risk models in predicting mortality and examined their utilization using data from a contemporary multinational registry. Background: Several prognostic risk scores have been developed for ambulatory HF patients, but their precision is still inadequate and their use limited. Methods: This registry enrolled patients with HF seen in participating European centers between May 2011 and April 2013. The following scores designed to estimate 1- to 2-year all-cause mortality were calculated in each participant: CHARM (Candesartan in Heart Failure-Assessment of Reduction in Mortality), GISSI-HF (Gruppo Italiano per lo Studio della Streptochinasi nell'Infarto Miocardico-Heart Failure), MAGGIC (Meta-analysis Global Group in Chronic Heart Failure), and SHFM (Seattle Heart Failure Model). Patients with hospitalized HF (n = 6,920) and ambulatory HF patients missing any variable needed to estimate each score (n = 3,267) were excluded, leaving a final sample of 6,161 patients. Results: At 1-year follow-up, 5,653 of 6,161 patients (91.8%) were alive. The observed-to-predicted survival ratios (CHARM: 1.10, GISSI-HF: 1.08, MAGGIC: 1.03, and SHFM: 0.98) suggested some overestimation of mortality by all scores except the SHFM. Overprediction occurred steadily across levels of risk using both the CHARM and the GISSI-HF, whereas the SHFM underpredicted mortality in all risk groups except the highest. The MAGGIC showed the best overall accuracy (area under the curve [AUC] = 0.743), similar to the GISSI-HF (AUC = 0.739; p = 0.419) but better than the CHARM (AUC = 0.729; p = 0.068) and particularly better than the SHFM (AUC = 0.714; p = 0.018). Less than 1% of patients received a prognostic estimate from their enrolling physician. Conclusions: Performance of prognostic risk scores is still limited and physicians are reluctant to use them in daily practice. The need for contemporary, more precise prognostic tools should be considered

Hypertensive disorders in women with peripartum cardiomyopathy: insights from the ESC EORP PPCM Registry

Aims: Hypertensive disorders occur in women with peripartum cardiomyopathy (PPCM). How often hypertensive disorders co-exist, and to what extent they impact outcomes, is less clear. We describe differences in phenotype and outcomes in women with PPCM with and without hypertensive disorders during pregnancy. Methods: The European Society of Cardiology PPCM Registry enrolled women with PPCM from 2012-2018. Three groups were examined: 1) women without hypertension (‘PPCM-noHTN’); 2) women with hypertension but without pre-eclampsia (‘PPCM-HTN’); 3) women with pre-eclampsia (‘PPCM-PE’). Maternal (6-month) and neonatal outcomes were compared. Results: Of 735 women included, 452 (61.5%) had PPCM-noHTN, 99 (13.5%) had PPCM-HTN and 184 (25.0%) had PPCM-PE. Compared to women with PPCM-noHTN, women with PPCM-PE had more severe symptoms (NYHA IV in 44.4% and 29.9%, p&lt;0.001), more frequent signs of heart failure (pulmonary rales in 70.7% and 55.4%, p=0.002), higher baseline LVEF (32.7% and 30.7%, p=0.005) and smaller left ventricular end diastolic diameter (57.4mm [±6.7] and 59.8mm [±8.1], p&lt;0.001). There were no differences in the frequencies of death from any cause, re-hospitalization for any cause, stroke, or thromboembolic events. Compared to women with PPCM-noHTN, women with PPCM-PE had a greater likelihood of left ventricular recovery (LVEF≥50%) (adjusted OR 2.08 95% CI 1.21-3.57) and an adverse neonatal outcome (composite of termination, miscarriage, low birth weight or neonatal death) (adjusted OR 2.84 95% CI 1.66-4.87). Conclusion: Differences exist in phenotype, recovery of cardiac function and neonatal outcomes according to hypertensive status in women with PPCM