Fibrosis is present in an important proportion of myocardial disorders. Injury activates cardiac fibroblasts, which deposit excess extracellular matrix, increasing tissue stiffness, impairing cardiac ...function, and leading to heart failure. Clinical therapies that directly target excessive fibrosis are limited, and more effective treatments are needed. Immunotherapy based on chimeric antigen receptor (CAR) T cells is a novel technique that redirects T lymphocytes toward specific antigens to eliminate the target cells. It is currently used in haematological cancers but has demonstrated efficacy in mouse models of hypertensive cardiac fibrosis, with activated fibroblasts as the target cells. CAR T cell therapy is associated with significant toxicities, but CAR natural killer cells can overcome efficacy and safety limitations. The use of CAR immunotherapy offers a potential alternative to current therapies for fibrosis reduction and restoration of cardiac function in patients with myocardial fibrosis.
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•New therapeutic approaches are needed to treat cardiac fibrosis.•CAR T cell immunotherapy has antifibrotic effect in cardiac fibrosis mouse models.•CAR NK cells could be an “off-the-shelf” therapy that avoids CAR T cell toxicity.
A significant proportion of patients develop atrial fibrillation (AF) following cavotricuspid isthmus (CTI) ablation for typical atrial flutter (AFl). The objective of this study was to assess ...whether the presence of advanced interatrial block (aIAB) was associated with an elevated risk of AF after CTI ablation in patients with typical AFl and no prior history of AF.
This study included patients with typical AFl and no prior history of AF that were referred for CTI ablation. Patients were excluded when they had received repeat ablations or did not demonstrate a bidirectional block. In all patients, a post-ablation electrocardiogram (ECG) in sinus rhythm was evaluated for the presence of aIAB, defined as a P-wave duration ≥120 ms and biphasic morphology in the inferior leads. New-onset AF was identified from 12-lead ECGs, Holter monitoring, and device interrogations. The cohort comprised 187 patients (age 67 ± 10.7 years; ejection fraction 55.8 ± 11.2%). Advanced interatrial block was detected in 18.2% of patients, and left atrium was larger in patients with aIAB compared with those without aIAB (46.2 ± 5.9 vs. 43.1 ± 6.0 mm; P = 0.01). Over a median follow-up of 24.2 months, 67 patients (35.8%) developed new-onset AF. The incidence of new-onset AF was greater in patients with aIAB compared with those without aIAB (64.7 vs. 29.4%; P < 0.001). After a comprehensive multivariate analysis, aIAB emerged as the strongest predictor of new-onset AF odds ratio (OR) 4.2, 95% confidence interval (CI): 1.9-9.3; P < 0.001.
Advanced interatrial block is a key predictor for high risk of new-onset AF after a successful CTI ablation in patients with typical AFl.
Arrhythmogenic right ventricular dysplasia or cardiomyopathy (ARVD/C) is a pathologic condition where the right ventricle is partially or totally replaced by fatty and fibrous tissue. The ...electrocardiogram (ECG) has a central role for diagnosis since it comprises two major and two minor criteria in the diagnostic criteria published by the Task 1 Force, although it is not 100% necessary to make a final diagnosis, because around 10% of patients with ARVD/C present with a normal ECG. In this article, we review the 12-lead electrocardiographic findings of patients with ARVD/C. ECG criteria observed during depolarization prolonged terminal activation duration, epsilon wave, partial right bundle branch block (RBBB) and advanced RBBB of peripheral origin with characteristic ECG patterns and repolarization abnormalities, (negative T waves) are reviewed in detail. More common ventricular arrhythmias and risk of sudden death, and how to use the surface ECG to stratify the risk, are part of our final comments.
There is limited information on the sex-specific longitudinal changes of left ventricular ejection fraction (LVEF) after an acute heart failure (AHF) hospitalization. We aimed to investigate whether ...LVEF trajectories over time and their impact on mortality and AHF readmission rates differ between men and women.
We conducted a retrospective sex-specific analysis of longitudinal LVEF measurements (n = 9581) in 3383 patients with an index hospitalization for AHF in a single tertiary-level hospital. Statistical techniques suited for longitudinal data analysis were used. The mean age of the sample was 73.8 ± 11.2 years, and 47.9% were women. The mean LVEF was 49.4 ± 15.3%. At a median follow-up of 2.58 years (interquartile range 0.77-5.62), we registered 2197 deaths (64.9%) and 2597 AHF readmissions in 1302 (38.5%) patients. The longitudinal analysis showed that women had consistently higher LVEF values throughout the follow-up with both trajectories characterized by an early peak-approximately at 1 year-followed by decreasing values in men but a plateau in women. Multivariate between-sex comparisons across LVEF categories revealed that women had lower rates of AHF readmissions when LVEF ≤40%. On the contrary, women displayed an excess risk of AHF readmissions when LVEF >60%. A trend in the same direction was found for cardiovascular and all-cause mortality.
Sex was a significant factor in determining the follow-up trajectory of LVEF and predicting differences in outcomes after an AHF admission. The findings suggest that women have a higher risk of AHF readmissions at higher LVEF values, while men have a higher risk at lower LVEF values. For all-cause and cardiovascular mortality, the same direction of the association was inferred but they were not significant.
Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with ...dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.
Aims
Heart failure (HF) outcomes remain poor despite optimal guideline‐directed medical therapy (GDMT). We assessed safety, effectiveness, and transthoracic echocardiographic (TTE) outcomes during ...the 12 months after Ventura shunt implantation in the RELIEVE‐HF open‐label roll‐in cohort.
Methods and results
Eligibility required symptomatic HF despite optimal GDMT with ≥1 HF hospitalization in the prior year or elevated natriuretic peptides. The safety endpoint was device‐related major adverse cardiovascular or neurological events at 30 days, compared to a prespecified performance goal. Effectiveness evaluations included the Kansas City Cardiomyopathy Questionnaire (KCCQ) at baseline, 1, 3, 6, and 12 months and TTE at baseline and 12 months. Overall, 97 patients were enrolled and implanted at 64 sites. Average age was 70 ± 11 years, 97% were in New York Heart Association class III, and half had left ventricular ejection fraction (LVEF) ≤40%. The safety endpoint was achieved (event rate 0%, p < 0.001). KCCQ overall summary score was improved by 12–16 points at all follow‐up timepoints (all p < 0.004), with similar outcomes in patients with reduced and preserved LVEF. At 12 months, left ventricular end‐systolic and end‐diastolic volumes were reduced (p = 0.020 and p = 0.038, respectively), LVEF improved (p = 0.009), right ventricular end‐systolic and end‐diastolic areas were reduced (p = 0.001 and p = 0.030, respectively), and right ventricular fractional area change (p < 0.001) and tricuspid annular plane systolic excursion (p < 0.001) improved.
Conclusion
Interatrial shunting with the Ventura device was safe and resulted in favourable clinical effects in patients with HF, regardless of LVEF. Improvements of left and right ventricular structure and function were consistent with reverse myocardial remodelling. These results would support the potential of this shunt device as a treatment for HF.
RELIEVE‐HF roll‐in cohort: study summary, findings, and possible mechanisms. BNP, brain natriuretic peptide; EF, ejection fraction; HF, heart failure; HFH, heart failure hospitalization; KCCQ, Kansas City Cardiomyopathy Questionnaire; LA, left atrium; LAP, left atrial pressure; LV, left ventricle; LVEDP, left ventricular end‐diastolic pressure; NYHA, New York Heart Association; NT‐proBNP, N‐terminal pro‐brain natriuretic peptide; PGA, Patient Global Assessment; RA, right atrium; RV, right ventricle.
Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with stroke, cognitive impairment, and cardiovascular death. Some predisposing factors - as aging, diabetes, ...hypertension - induce and maintain electrophysiological and ultrastructural remodeling that usually includes fibrosis. Interatrial conduction disturbances play a crucial role in the initiation of atrial fibrosis and in its associated complications. The diagnosis of interatrial blocks (IABs) is easy to perform using the surface ECG. IAB is classified as partial when the P wave duration is ≥120 ms, and advanced if the P wave also presents a biphasic pattern in II, III and aVF. IAB is very frequent in the elderly and, particularly in the case of the advanced type, is associated with AF, AF recurrences, stroke, and dementia. The anticoagulation in elderly patients at high risk of AF without documented arrhythmias is an open issue but recent data suggest that it might have a role, particularly in elderly patients with structural heart disease, high CHA
DS
VASc (Congestive heart failure/left ventricular dysfunction, Hypertension, Age ≥ 75 doubled, Diabetes, Stroke doubled - Vascular disease, Age 65-74, and Sex category female), and advanced IAB. In this debate, we discuss the association of surface ECG IAB, a marker of atrial fibrosis, with AF and stroke. We also present the rationale that justifies further studies regarding anticoagulation in some of these patients.
Background
Sodium‐glucose linked transporter 2 inhibition recently emerged as a promising therapy for reducing the risk of heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). ...However, there is a lack of data endorsing its role in symptomatic HF patients. We sought to evaluate the short‐term effects of empagliflozin on maximal exercise capacity in these patients.
Hypothesis
We postulate tretament with empagliflozin may improve functional capacity in patients with T2DM and established HF.
Methods
Nineteen T2DM patients with symptomatic HF were prospectively included and underwent cardiopulmonary exercise testing before and 30 days after initiation of empagliflozin therapy. A mixed‐effects model for repeated measures was used.
Results
Median patient age was 72 years (interquartile range, 60–79 years); 42.1% were in New York Heart Association class III. Baseline mean (± SD) peak oxygen consumption (peak VO2) was 10.9 ± 4.0 mL/min/kg. Peak VO2 increased significantly at 30 days (∆: +1.21 0.66 to 1.76 mL/min/kg; P < 0.001). A significant improvement in ventilatory efficiency during exercise, 6‐minute walking distance, and quality of life, and a reduction in antigen carbohydrate 125, were also found. Estimated glomerular filtration rate and natriuretic peptides did not significantly change.
Conclusions
In this pilot study, empagliflozin was associated with 1‐month improvement in exercise capacity in T2DM patients with symptomatic HF. This beneficial effect was also found for other surrogates of severity.
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