Epicardial adipose tissue, pulmonary veins anatomy, and the P-wave/PR interval ratio in young patients with atrial fibrillation.

Background: Atrial fibrillation (AF) is uncommon in the youngest population. Epicardial adipose tissue (EAT) volume has been proposed as an independent AF risk factor. Objective: The aim of this retrospective study was to evaluate the impact of the EAT, the anatomy of the pulmonary veins (PVs), and electrocardiogram (ECG) features in these young patients with AF. Methods: Sixty-two patients divided in 2 groups, one with history of paroxysmal AF treated with ablation and the other, a control group, all younger than 30 years of age, were included. Computed tomography scans were performed in both groups to estimate the PVs anatomy and EAT volume. Twelve-lead ECGs were performed in all patients. Patients underwent follow-up in our outpatient clinic (35.9 ± 18.3 months). Results: In the AF group, the EAT volume around the left atrium was 22.25 ± 9.3 cm3 compared with 12.61 ± 3.37 cm3, showing a statistically significance difference (P = .003). Family history resulted to be another significant risk factor (P = .009). During follow-up, 67.7% of the patients treated were still free of events. The anatomy and morphology of the right-sided PVs seemed to play a more consistent role in the patients with AF recurrences (P = .04). The P/PR ratio, a new ECG index, seemed predict AF recurrences after ablation (P = .03). Conclusion: The abundance of EAT seems related to the risk of developing AF in young patients. The recurrence of AF is about 33% and does not seem related to the EAT volume, but rather to the anatomy of the PVs. A higher P/PR ratio might suggest recurrences.

Aortic stiffness plays a role in the discrepancy between mitral valve lesion severity and hemodynamic burden of secondary mitral regurgitation.

BACKGROUND: By the framework of proportionate/disproportionate secondary mitral regurgitation (sMR), disproportionate sMR is characterized by a low left ventricular stroke volume (SV) and an out of proportion regurgitant fraction (RF) for the same effective regurgitant orifice area (EROA). The degree of aortic stiffness is a determinant of the ventricular forward SV. We aim to analyze the importance of aortic stiffness in influencing the discrepancy between measures of mitral valve lesion severity (EROA) and sMR hemodynamic burden (regurgitant volume [RV] and RF). METHODS: We enrolled stable patients with heart failure with reduced ejection fraction (HFrEF) and at least mild sMR. Mitral EROA, RV, RF and aortic pulse wave velocity (PWV) were measured by echocardiography. We defined three groups based on the degree of actual RF deviation from RF estimated by the linear regression equation of RF on EROA (concordant, low-discordant [residuals lower-than -5%] and high-discordant RF [residuals higher-than 5%]). RESULTS: 117 patients were analyzed (68±13 years; female 30%; LVEF 33±8%; EROA 16±12mm2; RV 24±15 ml; RF 27±13%; PWV 6.6 ± 3.2 m/s). LVEF, end-diastolic-volume and EROA didn't differ among groups. PWV and RV were higher in patients with high-discordant RF (p ≤ 0.01), whereas total left ventricular-SV and left ventricular outflow tract-SV (LVOT-SV) were lower (p ≤ 0.0004). PWV was associated with LVOT-SV (r=-0.3;p = 0.0008) and RV (r = 0.3;p = 0.0009). High-discordant RF was predicted by PWV (p = 0.001) independently of LVOT-SV and RV. CONCLUSION: In this HFrEF cohort with sMR, higher PWV was associated with higher-than-expected RF for a given EROA. Aortic stiffness might play a role in the discrepancy between mitral valve lesion severity and sMR hemodynamic burden.

Controlling nutritional status score predicts 2-year outcomes in elderly patients admitted for acute heart failure.

BACKGROUND: Heart failure (HF) is a major cause of death among the elderly. Its prevalence increases dramatically with age. The prevalence of malnourished subjects is high in hospitalized elderly patients. We aimed to investigate the prognostic role of malnutrition, assessed by controlling nutritional status (CONUT) score, on adverse clinical outcomes in the elderly admitted for acute HF. METHODS: We enrolled 293 patients (mean age 84 years; 48% men) consecutively admitted for acute HF to the Internal Medicine or Geriatrics Divisions at the 'IRCCS Sacro Cuore-Don Calabria' Hospital of Negrar (Verona, Italy) from 2013 to 2015. We predicted the risk of all-cause death, re-hospitalizations for HF and non-HF causes, and the composite of all-cause death or hospitalizations over 2-year follow-up. Patients were divided into four groups according to CONUT score: normal-CONUT (0-1; n = 30); mild-CONUT (2-3; n = 56); moderate-CONUT (4-7; n = 171); and severe-CONUT (≥ 8; n = 36). RESULTS: Higher CONUT scores were associated with older age and lower entry blood pressures. No difference in hemodynamics was noted at the discharge. Kaplan-Meier curves showed a significant association between worsening CONUT scores and risk of all-cause death (p < 0.01), re-hospitalizations (p < 0.01), or both (p < 0.001). Cox regression analysis revealed these significant associations persisted after adjustment for age, sex, pre-existing cardiovascular disease, diabetes, chronic kidney disease, heart rate, systolic blood pressure, and plasma brain natriuretic peptide levels at discharge (all-cause mortality HR = 1.29 (1.00-1.66), p = 0.049; hospitalization for HF HR = 1.36 (1.03-1.81), p = 0.033; hospitalization for non-HF HR = 1.38 (1.03-1.86), p = 0.034; composite outcome HR = 1.33 (1.07-1.64), p = 0.01). CONCLUSIONS: Malnutrition, assessed by the CONUT score, is common among elderly patients admitted for acute HF and is strongly related to increased long-term risk of all-cause death and re-hospitalizations.

Association between metabolic dysfunction-associated fatty liver disease and supraventricular and ventricular tachyarrhythmias in patients with type 2 diabetes.

BACKGROUND: Currently, it remains uncertain whether metabolic dysfunction-associated fatty liver disease (MAFLD) is associated with increased risk of supraventricular and ventricular tachyarrhythmias in people with type 2 diabetes mellitus (T2DM). METHODS: We retrospectively examined the data of 367 ambulatory patients with T2DM who underwent 24-hour Holter monitoring between 2015 and 2022 for clinical indications, and who did not have pre-existing permanent atrial fibrillation (AF), kidney failure or known liver diseases. Paroxysmal supraventricular tachycardia (PSVT), paroxysmal AF and episodes of ventricular tachyarrhythmias (i.e., presence of ventricular tachycardia, >30 premature ventricular complexes per hour, or both) were recorded. The presence and severity of MAFLD was diagnosed by ultrasonography and fibrosis-4 (FIB-4) index. RESULTS: Patients with T2DM who had MAFLD (n = 238) had a significantly greater prevalence of PSVT (51.7% vs. 38.8%), paroxysmal AF (6.3% vs. 1.3%) and combined ventricular tachyarrhythmias (31.9% vs. 20.2%) compared to their counterparts without MAFLD (n = 129). MAFLD was significantly associated with a greater than two-fold risk of having PSVT (adjusted-odds ratio [OR] 2.04, 95% confidence interval 1.04-4.00) or ventricular tachyarrhythmias (adjusted-OR 2.44, 95%CI 1.16-5.11), after adjusting for age, sex, smoking, alcohol intake, diabetes-related factors, comorbidities, medication use and left ventricular ejection fraction on echocardiography. The risk of supraventricular and ventricular tachyarrhythmias was even greater amongst patients with MAFLD and FIB-4 ≥ 1.3. CONCLUSIONS: In ambulatory patients with T2DM, the presence and severity of MAFLD was strongly associated with an increased risk of supraventricular and ventricular arrhythmias on 24-hour Holter monitoring.

Decline of Admission for Acute Coronary Syndromes and Acute Cardiovascular Conditions during COVID-19 Pandemic in Veneto Region.

Background: The present study aimed to examine longitudinal trends in hospitalizations for acute coronary syndrome (ACS) before and during the COVID-19 pandemic, by reviewing the data from 13 hospitals of the Veneto Region, in the north-east of Italy. Methods: We performed a multicenter, retrospective analysis including all the consecutive patients presenting with ACS and other acute cardiovascular (CV) conditions (defined as heart failure, arrhythmias, cardiac arrest and venous thromboembolism) hospitalized in 13 different hospitals of the Veneto Region covering a population of 2,554,818 inhabitants, during the first (between 15 March 2020 and 30 April 2020) and second (between 15 November 2020 and 30 December 2020) COVID-19 pandemic waves (the 2020 cohort). Data were compared with those obtained at the same time-windows of years 2018 and 2019 (the historical cohorts). Results: Compared to the historical cohorts, a significant decrease in the number of ACS cases was observed in 2020 (−27.3%, p = 0.01 and −32%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). The proportion of patients hospitalized for acute CV conditions decreased during the first and second wave COVID-19 pandemic when compared to the historical cohorts (−36.5%, p < 0.001 and −40.6%, p < 0.001, comparing 2018 versus 2020 and 2019 and 2020, respectively). Pearson's correlation evidenced a significant inverse relationship between the number of COVID-19 cases and both ACS hospital admissions (r = −0.881, p = 0.005) and hospitalizations for acute CV conditions (r = −0.738, p = 0.01), respectively. Conclusions: The decrease in hospitalizations for ACS and other acute CV conditions will strongly affect future patients' management since undiagnosed nonfatal CV events represent a source of increased (and unknown) CV morbidity and mortality.

Takotsubo Syndrome during COVID-19 Pandemic in the Veneto Region, Italy.

Background: During the COVID-19 pandemic, the risk of SARS-CoV-2 infection, the public health measures of social distancing, the freedom limitations, quarantine, and the enforced homeworking under the lockdown period, as well as medical causes including COVID-19 infection per se, may have caused major emotional distress, especially in the most vulnerable patients. We aimed to evaluate the variations in the number of admissions due to Takotsubo syndrome (TTS) during the COVID-19 pandemic in the Veneto region. Methods: We retrospectively reviewed and analyzed the number of admissions because of TTS in 13 Divisions of Cardiology located in the Veneto region, the northeastern area of Italy, covering a population of more than 2.5 million inhabitants, during the two major pandemic waves of COVID-19 (the first between 15 March and 30 April 2020 and the second between 15 November and 30 December 2020) that occurred in 2020. Results: In total, 807 acute coronary syndromes were admitted in the 13 enrolling hospitals. Among these, 3.9% had TTS. Compared to the corresponding 2018 and 2019 time periods, we observed a significant increase in the number of TTS cases (+15.6%, p = 0.03 and +12.5%, p = 0.04, comparing 2018 to 2020 and 2019 to 2020, respectively). Geographical distribution of the TTS cases reflected the broad spread of the SARS-CoV-2 infection with a significant direct relationship between TTS incidence and the number of COVID-19 infections according to Pearson's correlation (r = 0.798, p < 0.001). Conclusions: The higher incidence of TTS during the 2020 COVID-19 pandemic waves, especially in the areas that were hit hardest in terms of morbidity and mortality by the SARS-CoV-2 infection, suggest a strong direct and/or indirect role of COVID-19 in the pathogenesis of TTS.

Non-alcoholic fatty liver disease and risk of new-onset heart failure: an updated meta-analysis of about 11 million individuals.

OBJECTIVE: Recent studies reported an association between non-alcoholic fatty liver disease (NAFLD) and increased risk of new-onset heart failure (HF). However, the magnitude of the risk and whether this risk changes with severity of liver disease remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between NAFLD and risk of new-onset HF. DESIGN: We systematically searched Scopus, Web of Science and PubMed from database inception to March 2022 to identify eligible observational studies, in which NAFLD was diagnosed by serum biomarkers/scores, International Classification of Diseases (ICD) codes, imaging techniques or liver histology. The primary outcome was new-onset HF, as assessed mainly by ICD codes. Data from selected studies were extracted, and meta-analysis was performed using random-effects models to obtain summary hazard ratios (HRs) with 95% CIs. RESULTS: We identified 11 longitudinal cohort studies with aggregate data on 11 242 231 middle-aged individuals from different countries and 97 716 cases of incident HF over a median of 10 years. NAFLD was associated with a moderately higher risk of new-onset HF (pooled random-effects hazard ratio 1.50, 95% CI 1.34 to 1.67, p<0.0001; I 2=94.8%). This risk was independent of age, sex, ethnicity, adiposity measures, diabetes, hypertension and other common cardiovascular risk factors. Sensitivity analyses did not change these results. The funnel plot did not show any significant publication bias. CONCLUSION: NAFLD is associated with a 1.5-fold higher long-term risk of new-onset HF, regardless of the presence of diabetes, hypertension and other common cardiovascular risk factors. However, the observational design of the studies does not allow for proving causality.

Association between Higher Circulating Leucine-Rich α-2 Glycoprotein 1 Concentrations and Specific Plasma Ceramides in Postmenopausal Women with Type 2 Diabetes.

Background: Although ceramides are involved in the pathophysiology of cardiovascular disease and other inflammation-associated disorders, there is a paucity of data on the association between plasma ceramides and inflammatory biomarkers in type 2 diabetes mellitus (T2DM). Therefore, we explored whether there was an association between plasma leucine-rich α-2 glycoprotein 1 (LRG1) concentrations (i.e., a novel proinflammatory signaling molecule) and specific plasma ceramides in postmenopausal women with T2DM. Methods: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)], amongst 99 Caucasian postmenopausal women with non-insulin-treated T2DM (mean age 72 ± 8 years, mean hemoglobin A1c 6.9 ± 0.7%), who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramide and LRG1 concentrations were measured with a targeted liquid chromatography-tandem mass spectrometry assay and a Milliplex® MAP human cardiovascular disease magnetic bead kit, respectively. Results: In linear regression analyses, higher plasma LRG1 levels (1st tertile vs. 2nd and 3rd tertiles combined) were associated with higher levels of plasma Cer(d18:1/16:0) (standardized ß coefficient: 0.289, p = 0.004), Cer(d18:1/18:0) (standardized ß coefficient: 0.307, p = 0.002), Cer(d18:1/20:0) (standardized ß coefficient: 0.261, p = 0.009) or Cer(d18:1/24:1) (standardized ß coefficient: 0.343, p < 0.001). These associations remained significant even after adjusting for age, body mass index, systolic blood pressure, total cholesterol level, hemoglobin A1c, insulin resistance and statin use. Conclusions: The results of our pilot exploratory study suggest that higher plasma LRG1 concentration was associated with higher levels of specific high-risk plasma ceramide molecules in elderly postmenopausal women with metabolically well-controlled T2DM, even after adjusting for known cardiovascular risk factors and other potential confounding variables.

Stereotactic ablative radiotherapy in patients with refractory ventricular tachyarrhythmia.

Stereotactic ablative body radiotherapy (SABR) is an innovative therapeutic approach in patients (pts) with a diagnosis of refractory ventricular tachyarrhythmia (VT) after the use of drugs, radiofrequency catheter ablation, and/or defibrillator (ICD) implant. The current efficacy data of SABR are limited and several prospective clinical studies are ongoing to support the use of ablative radiation dose to control VT. The aim of the current prospective pilot study is to report the efficacy and tolerability of SABR in ICD implanted pts with refractory VT in our centre. Non-invasive electroanatomical mapping (EAM), cardiac computed tomography (CT), and 18F-fluorodeoxyglucose positron emission (FDG-PET)-CT scan were used and combined with a radiation CT scan. A dose prescription of 25 Gy in a single dose was delivered by volumetric modulated arc therapy (VMAT) Linac-based. The primary endpoint was efficacy, defined as a reduction in ICD shocks after SABR treatment, while the secondary endpoint was safety. Six consecutive pts (five males and one female) implanted with an ICD and with three or more VT were enrolled. One pts died after 1 month, due to end-stage heart failure. Two pts experienced ICD shocks in VT 2 and 5 months after treatment. Three pts experienced no more ICD shocks on VT after therapy. Our data suggest the efficacy and safety of SABR treatment in pts with VT. Larger dataset of pts and longer follow-up are otherwise required to validate the impact of SABR as a standardized treatment in these pts.

Association between KLF6 rs3750861 polymorphism and plasma ceramide concentrations in post-menopausal women with type 2 diabetes.

BACKGROUND AND AIM: Based on the emerging role of Kruppel-like factor 6 (KLF6) in lipid metabolism, we examined whether there is a relationship between the KLF6 rs3750861 genetic variant and plasma ceramide levels in people with type 2 diabetes mellitus (T2DM). METHODS AND RESULT: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)] amongst 101 Caucasian post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramides were measured by targeted liquid chromatography-tandem mass spectrometry assay. Genotyping of the KLF6 rs3750861 polymorphism was performed by TaqMan-Based RT-PCR system. Overall, 87 (86.1%) patients had KLF6 rs3750861 C/C genotype and 14 (13.9%) had C/T or T/T genotypes. After adjustment for age, diabetes-related variables, use of lipid-lowering drugs and other potential confounders, patients with C/T or T/T genotypes had higher plasma Cer(d18:1/18:0) (0.159 ± 0.05 vs. 0.120 ± 0.04 µmol/L, p = 0.012), Cer(d18:1/20:0) (0.129 ± 0.04 vs. 0.098 ± 0.03 µmol/L, p = 0.008), and Cer(d18:1/24:1) (1.236 ± 0.38 vs. 0.978 ± 0.36 µmol/L, p = 0.032) compared with those with C/C genotype. CONCLUSIONS: The C/T or T/T genotypes of rs3750861 in the KLF6 gene were closely associated with higher levels of specific plasma ceramides in post-menopausal women with T2DM.

Association between higher serum uric acid levels and plasma N-terminal pro-B-type natriuretic peptide concentrations in patients with coronary artery disease and without overt heart failure.

BACKGROUND: The association between serum uric acid (SUA) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations in patients with coronary artery disease (CAD) is unclear. METHODS: We retrospectively studied 171 patients with suspected or established CAD and without overt heart failure who were consecutively admitted to our Division of Cardiology from February to August 2016. Plasma NT-proBNP concentrations were measured using a chemiluminescent immunoassay method. A conventional echocardiography and coronary angiogram were also performed in all patients. RESULTS: Patients in the 3rd SUA tertile had higher median plasma NT-proBNP concentrations compared with those belonging to 2nd or 1st SUA tertile, respectively (443 [IQR: 222-1381] vs. 224 [99-487] vs. 162 [68-307] pg/mL; p < 0.001). After adjustment for age, sex, body mass index, hypertension, diabetes, chronic kidney disease, prior ischemic heart disease, prior heart failure, medication use, and left ventricular ejection fraction (LVEF), patients belonging to the 3rd SUA tertile had an increased risk of higher plasma NT-proBNP concentrations (adjusted-standardized beta coefficient: 0.310, p < 0.001). Almost identical results were found when patients treated with allopurinol (n = 14), or those with prior HF (n = 8) were excluded from the analyses. CONCLUSIONS: These results show that increased SUA levels are strongly associated with higher plasma NT-proBNP concentrations in patients with suspected or established CAD and without overt heart failure, independent of established cardiovascular risk factors, LVEF, medication use and other potential confounders.

Risk of Heart Failure in Patients With Nonalcoholic Fatty Liver Disease: JACC Review Topic of the Week.

Heart failure (HF) and nonalcoholic fatty liver disease (NAFLD) are 2 conditions that have become important global public health problems. Emerging evidence supports a strong and independent association between NAFLD and the risk of new-onset HF, and there are multiple potential pathophysiological mechanisms by which NAFLD may increase risk of new-onset HF. The magnitude of this risk parallels the underlying severity of NAFLD, especially the level of liver fibrosis. Patients with NAFLD develop accelerated coronary atherosclerosis, myocardial alterations (mainly cardiac remodeling and hypertrophy), and certain arrhythmias (mainly atrial fibrillation), which may precede and promote the development of new-onset HF. This brief narrative review aims to provide an overview of the association between NAFLD and increased risk of new-onset HF, discuss the underlying mechanisms that link these 2 diseases, and summarize targeted pharmacological treatments for NAFLD that might also reduce the risk of HF.