Improving Diagnosis and Treatment in Heart Failure and Myocarditis

Background: Prior studies evaluating post-atrial fibrillation (AF) ablation pulmonary vein (PV) ostial gaps via magnetic resonance imaging (MRI) have shown circumferential PV fibrosis in a minority of patients, and their correlation with AF recurrence was weak. These studies were mostly based on radio-frequency AF ablations. Aim: We aimed to assess cryoballoon ablation-induced PV fibrosis via MRI and its correlation with AF recurrence. Methods and Results: This was a prospective study of consecutive patients with symptomatic AF who underwent pre- and post-ablation MRI to assess baseline and ablation-induced fibrosis, respectively. Post-ablation PV gaps were assessed by new semi-quantitative visual analysis assisted by computerized ADAS analysis. AF recurrence monitored via multiple ECGs and event monitoring at 6 and 12 months post ablation. Nineteen patients with 80 PVs were included, age 56 ± 11, with paroxysmal and persistent AF in 17/19 and 2/19 patients, respectively. Baseline MRI showed minimal LA fibrosis. All patients underwent successful cryoballoon PV electrical isolation. Post-ablation MRI revealed circumferential PV fibrosis among 63/80 (78.8%) PVs and partial fibrosis with major gaps among 17/80 (21.2%) PVs. AF recurred within one year in 5/9 (55.5%) patients with partial PV fibrosis, while no AF recurred among the 10 patients in whom all PVs had circumferential fibrosis (p < 0.01). Similarly, there were significantly more PVs without circumferential fibrosis (due to major gaps) among patients with AF recurrence as compared with patients without AF recurrence (42.9% vs. 13.5%; p < 0.01). Conclusion: Cryoballoon AF ablation results in circumferential PV fibrosis in the majority of PVs, as assessed by a new clinically relevant MRI-LGE analysis. Significant correlation was found between major PV gaps on post-ablation MRI and AF recurrence, suggesting that MRI might have the ability to predict AF recurrence. Full article

Background: Cardiac amyloidosis (CA) could be a common cause of heart failure (HF). The objective of the study was to estimate the prevalence of CA in patients with HF. Methods: Observational, prospective, and multicenter study involving 30 Spanish hospitals. A total of 453 patients ≥ 65 years with HF and an interventricular septum or posterior wall thickness > 12 mm were included. All patients underwent a ^99mTc-DPD/PYP/HMDP scintigraphy and monoclonal bands were studied, following the current criteria for non-invasive diagnosis. In inconclusive cases, biopsies were performed. Results: The vast majority of CA were diagnosed non-invasively. The prevalence was 20.1%. Most of the CA were transthyretin (ATTR-CM, 84.6%), with a minority of cardiac light-chain amyloidosis (AL-CM, 2.2%). The remaining (13.2%) was untyped. The prevalence was significantly higher in men (60.1% vs 39.9%, p = 0.019). Of the patients with CA, 26.5% had a left ventricular ejection fraction less than 50%. Conclusions: CA was the cause of HF in one out of five patients and should be screened in the elderly with HF and myocardial thickening, regardless of sex and LVEF. Few transthyretin-gene-sequencing studies were performed in older patients. In many patients, it was not possible to determine the amyloid subtype. Full article

Background: We investigated the role of the dynamic changes of pulmonary congestion, as assessed by sonographic B-lines, as a tool to stratify prognosis in patients admitted for acute heart failure with reduced and preserved ejection fraction (HFrEF, HFpEF). Methods: In this multicenter, prospective study, lung ultrasound was performed at admission and before discharge by trained investigators, blinded to clinical findings. Results: We enrolled 208 consecutive patients (mean age 76 [95% confidence interval, 70–84] years), 125 with HFrEF, 83 with HFpEF (mean ejection fraction 32% and 57%, respectively). The primary composite endpoint of cardiovascular death or HF re-hospitalization occurred in 18% of patients within 6 months. In the overall population, independent predictors of the occurrence of the primary endpoint were the number of B-lines at discharge, NT-proBNP levels, moderate-to-severe mitral regurgitation, and inferior vena cava diameter on admission. B-lines at discharge were the only independent predictor in both HFrEF and HFpEF subgroups. A cut-off of B-lines > 15 at discharge displayed the highest accuracy in predicting the primary endpoint (AUC = 0.80, p < 0.0001). Halving B-lines during hospitalization further improved event classification (continuous net reclassification improvement = 22.8%, p = 0.04). Conclusions: The presence of residual subclinical sonographic pulmonary congestion at discharge predicts 6-month clinical outcomes across the whole spectrum of acute HF patients, independent of conventional biohumoral and echocardiographic parameters. Achieving effective pulmonary decongestion during hospitalization is associated with better outcomes. Full article

Background and Objectives: Heart failure is a chronic disease with a high risk of mortality and morbidity. In these patients, inflammatory markers have been shown to be associated with cardiovascular adverse outcomes and disease progression. To investigate the relationships between eosinophil indices and major cardiovascular events (MACE) in patients with acute decompensated heart failure (ADHF) with reduced ejection fraction. Materials and Methods: A total of 395 consecutive patients admitted to the intensive care unit (ICU) with ADHF and reduced ejection fraction between January 2017 and December 2021 were enrolled in this retrospective study. MACE was defined as the composite of death and re-hospitalization for ADHF within 6 months of index hospitalization. All-cause mortality and MACE were assessed with respect to relationships with eosinophil indices, including neutrophil-to-eosinophil ratio (NER), leukocyte-to-eosinophil ratio (LER), eosinophil-to-lymphocyte ratio (ELR), and eosinophil-to-monocyte ratio (EMR). Results: NER and LER were significantly higher in subjects with MACE. Absolute eosinophil, lymphocyte and basophil count, hemoglobin, serum Na⁺, albumin, and CRP, and EMR and ELR were significantly lower in subjects with MACE compared to those without. NT-proBNP (OR: 1.682, 95% CI: 1.106–2.312, p = 0.001), Na⁺ (OR: 0.932, 95% CI: 0.897–0.969, p < 0.001), NER (OR: 2.740, 95 % CI: 1.797–4.177, p < 0.001), LER (OR: 2.705, 95% CI: 1.752–4.176, p < 0.001), EMR (OR:1.654, 95% CI 1.123–2.436, p = 0.011), ELR (OR: 2.112, 95% CI 1.424–3.134, p < 0.001), and eosinophil count (OR: 1.833, 95% CI 1.276–2.635) were independent predictors for development of MACE. Conclusions: Patients with ADHF and reduced ejection fraction who developed MACE within the first six months of index hospitalization had lower levels of absolute eosinophil and lymphocyte counts, and EMR and ELR values, whereas NER and LER were higher compared to those without MACE. The eosinophil indices were independently associated with mortality and MACE development. The eosinophil indices may be used to estimate MACE likelihood with acceptable sensitivity and specificity. Full article

Aims: The aim of this study was to evaluate the impact of sacubitril/valsartan on left ventricular (LV) reverse remodeling, potentially modifying the timing for cardiac device implantation in heart failure with reduced ejection fraction (HFrEF), which has not been specifically addressed. Methods and results: A secondary data analysis of a prospective cohort of HFrEF patients was conducted. Inclusion criteria: patients who started sacubitril/valsartan between November 2017 and August 2019 after previous optimal medical therapy. Primary endpoint: time to achieve LV Ejection Fraction (EF) > 35%. Kaplan–Meier was used to estimate median time and Cox regression model to investigate the patients’ characteristics associated with event incidence rate. In total, 48 patients were included, with a mean age of 72.5 years, predominantly male (70.8%). From the initial 48 patients with LVEF ≤ 35%, 27 (56%) reached LVEF > 35%, in a median time of 11.3 months (95% confidence interval [95%CI]: 9.4–19.6). In multivariate analysis, baseline LVEF between 30 and 35% was associated with increased cumulative incidence of attaining LVEF > 35% (Incidence rate ratio = 3.9; 95%CI: 1.6–9.9; p-value = 0.004). Conclusion: We observed an improvement in LVEF to >35% in the majority of patients who switched to sacubitril/valsartan, illustrating its role in cardiac remodeling. We speculate that this improvement may allow delaying implantation of Cardioverter-Defibrillator/Cardiac Resynchronization Therapy. Full article

We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03–1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05–1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients. Full article

Aims: While it is common practice to use intravenous (IV) iron in patients with left ventricular assist devices (LVADs) and iron deficiency, there is insufficient evidence regarding outcomes in this patient population. We evaluated the safety and effectiveness of IV iron therapy in patients supported by LVADs with iron deficiency. Methods: We performed a retrospective analysis of iron deficient patients on continuous LVAD support at a large academic center between 2008 and 2019. Patients were divided into two cohorts based on IV iron sucrose treatment. The primary endpoint was hemoglobin at 12 weeks. Secondary endpoints were mean corpuscular volume (MCV) and New York Heart Association (NYHA) class at 12 weeks. Safety endpoints included hospitalization, infection, pump thrombosis, arrhythmia, and gastrointestinal bleed. Models were weighted by the inverse probability of receiving IV iron using a propensity score, and endpoints were adjusted for their corresponding baseline values. Results: Among 213 patients, 70 patients received IV iron and 143 patients did not. Hemoglobin at 12 weeks was significantly greater among those treated (intergroup difference: 0.6 g/dL; 95% CI, 0.1 to 1.1; p = 0.01), while MCV was similar in both groups (intergroup difference: 0.7 μm³; 95% CI, −1.3 to 2.7; p = 0.50). NYHA class distribution at 12 weeks was significantly different (odds ratio for improvement: 2.84; 95% CI, 1.42 to 4.68; p = 0.003). The hazards of adverse events in each group were similar. Conclusions: In patients with LVADs and iron deficiency, treatment with IV iron sucrose was safe and associated with improvements in functional status and hemoglobin. Full article

The mobile cardiac acoustic monitoring system is a promising tool to enable detection and assist the diagnosis of left ventricular systolic dysfunction (LVSD). The objective of the study was to evaluate the diagnostic value of electromechanical activation time (EMAT), an important cardiac acoustic biomarker, in quantifying LVSD among left bundle branch pacing (LBBP) and right ventricular apical pacing (RVAP) patients using a mobile acoustic cardiography monitoring system. In this prospective single-center observational study, pacemaker-dependent patients were consecutively enrolled. EMAT, the time from the start of the pacing QRS wave to first heart sound (S1) peak; left ventricular systolic time (LVST), the time from S1 peak to S2 peak; and ECG were recorded simultaneously by the mobile cardiac acoustic monitoring system. LVEF was measured by echocardiography. A logistic regression model was applied to evaluate the association between EMAT and reduced EF (LVEF < 50%). A total of 105 pacemaker-dependent patients participated. The RVAP group (n = 58) displayed a significantly higher EMAT than the LBBP group (n = 47) (150.95 ± 19.46 vs. 108.23 ± 12.26 ms, p < 0.001). Pearson correlation analysis revealed a statistically significant negative correlation between EMAT and LVEF (p < 0.001). Survival analysis showed the sensitivity and specificity of detecting LVEF to be < 50% when EMAT ≥ 151 ms were 96.00% and 96.97% in the RVAP group. In LBBP patients, the sensitivity and specificity of using EMAT ≥ 110 ms as the cutoff value for the detection of LVEF < 50% were 75.00% and 100.00%. There was no significant difference in LVST with or without LVSD in the RVAP group (p = 0.823) and LBBP group (p = 0.086). Compared to LVST, EMAT was more helpful to identify LVSD in pacemaker-dependent patients. The cutoff point of EMAT for diagnosing LVEF < 50% differed regarding the pacing type. Therefore, the mobile cardiac acoustic monitoring system can be used to identify the progress of LVSD in pacemaker patients. Full article

We report an autopsy case of a 69-year-old female with cervical cancer. She was given bevacizumab-containing chemotherapy for 4 months. After two years of chemotherapy, she developed congestive heart failure (CHF) with left ventricular dysfunction. Cardiac magnetic resonance (CMR) imaging revealed late gadolinium enhancement (LGE) of linear mid-wall delayed enhancement located in the basal to the mid-septal wall, suggesting bevacizumab-related cardiotoxicity. Although she was treated with cardioprotective medications and discharged, she eventually died from worsening CHF a year later, and we conducted an autopsy. Histopathological examination revealed diffuse fibrosis in the myocardium, and the area where LGE was present on CMR showed thinning and wavy changes in cardiomyocytes with diffuse interstitial fibrosis and edema. Full article

Guideline-directed medical therapy (GDMT) is crucial in reducing mortality in patients with heart failure with heart rate lowering by a beta blocker (BB) being an important therapeutic concept. We aimed to assess the usefulness of a wearable cardioverter/defibrillator (WCD) to provide detailed information about heart rate for managing patients with reduced left ventricular ejection fraction (LVEF) and symptoms of heart failure and to correlate mortality with the mean heart rate. A total of 4509 consecutive patients (mean age: 59 + 13 years, 88% male) were analyzed retrospectively. All patients had reduced LVEF and were prescribed a WCD for protection from sudden cardiac death (SCD) during GDMT uptitration awaiting LVEF recovery. The device continuously measured nighttime and daytime HR at the beginning and end of WCD use. Patients who died during wear time had significantly higher HRs compared with survivors: daytime beginning of use (BOU), 80 ± 15 bpm vs. 76 ± 13, p < 0.01; nighttime BOU, 76 ± 14 vs. 69 ± 13, p < 0.0001; daytime end of use (EOU), 84 ± 20 vs. 73 ± 13, p < 0.0001; nighttime EOU, 80 ± 20 vs. 65 ± 12, p < 0.0001). In conclusion, HR monitoring with a WCD yields important prognostic information and may assist in optimal usage of BB in patients with low LVEF. Full article

Background: Information regarding short-term vital prognosis in patients with heart failure at advanced stages of the disease is scarce. Objective: To develop a three-month mortality predictive model for patients with advanced heart failure. Methods: Prospective observational study carried out in primary care and a convalescence community facility. Heart failure patients either New York Heart Association (NYHA) III with at least two HF hospitalizations during the previous six months or NYHA IV with/without previous recent hospitalization were included in the study. Multivariable predictive models using Cox regression were performed. Results: Of 271 patients included, 55 (20.3%) died during the first three months of follow-up. Mean age was 84.2 years (SD 8.3) and 59.8% were women. Predictive model including NT-proBNP had a C-index of 0.78 (95% CI 0.71; 0.85) and identified male gender, low body mass index, high potassium and NT-proBNP levels, and moderate-to-severe dependence for daily living activities (Barthel index < 40) as risk factors of mortality. In the model without NT-proBNP, C index was 0.72 (95% CI 0.64; 0.79) and, in addition to gender, body mass index, low Barthel index, and severe reductions in glomerular filtration rate showed the highest predictive hazard ratios for short-term mortality. Conclusions: In addition to age, male gender, potassium levels, low body mass index, and low glomerular filtration, dependence for activities of daily living add strong power to predict mortality at three months in patients with advanced heart failure. Full article

Background: Heart failure (HF) patients with wide QRS often benefit from cardiac resynchronization therapy (CRT), although QRS narrowing does not always occur. The current study investigates the incidence and predictors for QRS narrowing following CRT and its long-term impact on clinical outcomes. Methods: Among individuals undergoing clinically indicated CRT, pre-and post-implantation electrocardiographs were meticulously analyzed for QRS duration change. All-cause mortality and the composite of mortality and HF hospitalizations were retrieved. Results: For 104 patients, mean age 67 years, 25% females, QRS narrowed within days by 20.2 ± 24.7 ms. In 55/104 (53%) QRS narrowed by ≥20 ms (“acute narrowing”). Female gender and baseline QRS predicted acute narrowing. Acute narrowing persisted for 1–6 weeks in 18/20 (90%) and 3–12 months in 21/31 (68%) of patients. During the average follow-up of 41 months, 29/104 (28%) died and 50/104 (48%) met the composite outcome. In a multivariable analysis including comorbidities and cardiac history, prolonged baseline PR interval (HR 1.015, CI 1.008–1.021, p < 0.001) and acute narrowing < 20 ms (HR 3.243, CI 1.593–6.603, p = 0.001) were significant and independent predictors for the composite outcome. Conclusions: Post-CRT acute QRS narrowing ≥ 20 ms is independently associated with favorable long-term outcomes and might be considered as a novel measure for procedural success. Full article