Impact of initiation of SGLT2 inhibitor treatment on the development of arrhythmias in patients with implantable cardiac devices.

INTRODUCTION AND OBJECTIVES: Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) have been associated with improved prognosis in patients with heart failure, but their impact on atrial arrhythmic (AA) and ventricular arrhythmic (VA) events is not fully understood. METHODS: This multicenter retrospective study included patients with implantable cardioverter-defibrillators who initiated treatment with SGLT2i. AA and VA events were compared in 2 time periods for each patient: 1 year before and 1 year after starting SGLT2i. RESULTS: The study included 195 patients (66.8 [61.3-73.1] years, 18.5% women). In the post-SGLT2i period, there was a reduction in the percentage of patients with any VA (pre: 52.3% vs post: 30.3%; P<.001) and clinically relevant VA (excluding nonsustained ventricular tachycardia) (pre: 21.5% vs post: 8.7%; P<.001). There was also a decrease in the number of episodes per patient/y of nonsustained ventricular tachycardia (pre: 2 (1-5) vs post: 1 (0-2); P<.001) and sustained ventricular tachycardia (pre: 1 (1-3) vs post: 0 (0-2); P=0.046). However, no differences were observed in the prevalence of AA (24.7% vs 18.8%; P=.117) or the burden of atrial fibrillation (pre: 0% (0-0.1) vs post: 0% (0-0); P=.097). CONCLUSIONS: Initiation of SGLT2i treatment was associated with a decrease in the percentage of patients with relevant VA but this effect was not observed for AA.

Role of Soluble ST2 Biomarker in Predicting Recurrence of Atrial Fibrillation after Electrical Cardioversion or Pulmonary Vein Isolation.

This study aims to determine the predictive value of the soluble suppression of tumorigenicity 2 (sST2) biomarker in atrial fibrillation (AF) recurrence. This prospective, observational study included patients with AF referred for electrical cardioversion (ECV) or pulmonary vein isolation (PVI) procedures. Baseline characteristics were collected, and sST2 was determined at baseline and at 3 and 6 months of follow-up. sST2 was determined at baseline in a matched control group. Left atrial voltage mapping was performed in patients undergoing PVI. The sST2 maximal predictive capacity of AF recurrence was at the 3-month FU in the cohort of patients undergoing ECV with respect to 6-month AF recurrence with an AUC of 0.669, a cut-off point of 15,511 pg/mL, a sensitivity of 60.97%, and a specificity of 69.81%. The ROC curve of the sST2 biomarker at baseline and 3 months in the cohort of patients undergoing PVI showed AUCs of 0.539 and 0.490, respectively. The logistic regression model identified the rhythm (AF) and the sST2 biomarker at 3 months as independent factors for recurrence at 6 months in the ECV cohort. In the logistic regression model, sST2 was not an independent factor for recurrence at 6 months of follow-up in the PVI cohort. In patients who underwent ECV, sST2 values at 3 months may provide utility to predict AF recurrence at 6 months of follow-up. In patients who underwent PVI, sST2 had no value in predicting AF recurrence at 6 months of follow-up.

Atrial fibrillation ablation in patients with arrhythmia-induced cardiomyopathy: a prospective multicentre study.

AIMS: This study aims to investigate the clinical and biochemical characteristics of patients with atrial fibrillation (AF) referred for ablation who develop arrhythmia-induced cardiomyopathy (AiCM) as well as their long-term outcomes after catheter ablation (CA). METHODS AND RESULTS: A prospective multicentre study was conducted on consecutive AF patients who underwent CA. AiCM was defined as the development of heart failure in the presence of AF and an improvement of left ventricular fraction by at least 10% at 6 months after ablation. A subgroup of patients underwent peripheral and left atrial blood samples [galectin-3, fatty acid-binding protein 4 (FABP4), and soluble receptor for advanced glycation end products (sRAGE)] at the time of the procedure. Of the 769 patients who underwent AF ablation, 135 (17.56%) met the criteria for AiCM. Independent predictors of AiCM included persistent AF, male gender, left atrial volume, QRS width, active smoking, and chronic kidney disease (CKD). Biomarker analysis revealed that sRAGE, FABP4, and galectin-3 levels were not predictive of AiCM development nor did they differ between groups or predict recurrence. There were no differences in AF recurrence between patients with and without AiCM (30.83% vs. 27.77%; P = 0.392) during a median follow-up of 23.83 months (inter-quartile range 9-36). CONCLUSIONS: In the subset of patients referred for AF ablation, the development of AiCM was associated with persistent AF and CKD. Biomarker analysis was not different between groups nor predicted recurrence. Patients with AiCM benefited from ablation, with a significant improvement in left ventricular ejection fraction and similar AF recurrence rates to those without AiCM.

Effects of guideline-directed medical therapy in patients with left bundle branch block-induced cardiomyopathy.

INTRODUCTION AND OBJECTIVES: Left bundle branch block (LBBB)-induced cardiomyopathy occurs in patients with long-standing LBBB. These patients characteristically exhibit hyperresponsiveness to cardiac resynchronization therapies (CRT). However, there is scarce information on their response to medical treatment. The aim of this study was to assess the change in left ventricular ejection fraction (LVEF) after a 3-month period following titration of guideline-directed medical therapy for heart failure. METHODS: This retrospective analysis included all patients assessed in the heart failure unit of a Spanish University Hospital between 2020 and 2021, who presented with de novo ventricular dysfunction (LVEF <40%) and had a history of long-standing LBBB with no other possible causes of cardiomyopathy. RESULTS: A total of 1497 patients were analyzed, of which 21 were finally eligible. Mean time from first diagnosis of LBBB to first consultation was 4.05± 4.1 years. Mean LVEF from first consultation to end of titration improved from 29.5±5.7% to 32.7±8.6% (P = .172), but none had recovered ventricular function at the end of follow-up. New York Heart Association functional class improved from 1.91±0.46 to 1.81±0.53 (P=.542). After CRT device implantation in 8 patients, LVEF improved by 18.1±6.4% (P=.003). CONCLUSIONS: Guideline-directed medical therapy seems to be ineffective in improving LVEF and functional class in patients with de novo heart failure and LBBB-induced cardiomyopathy. Based on a positive response to CRT on LVEF improvement, early CRT implantation could be a reasonable strategy for these patients.

Relationship between Aldehyde Dehydrogenase, PD-L1 and Tumor-Infiltrating Lymphocytes with Pathologic Response and Survival in Breast Cancer.

Aldehyde dehydrogenase 1A1 (ALDH1A1) is a cancer stem cell (CSC) marker related to clinical outcomes in breast cancer (BC). The aim of this study was to analyze the relationship between ALDH1A1, programmed death ligand 1 (PD-L1) and tumor-infiltrating lymphocytes (TILs) in triple negative (TN) and human epidermal growth factor receptor 2-positive (HER2+) BC tumors, and its association with clinicopathological characteristics and outcomes. A retrospective, historical cohort study of patients diagnosed with early or locally advanced BC treated with neoadjuvant chemotherapy was conducted. ALDH1A1, PD-L1 expression and TILs were assessed using immunohistochemistry. A total of 75 patients were analyzed (42.7% TN, 57.3% HER2+ tumors). ALDH1A1+ was related to HTILs (p = 0.005) and PD-L1+ tumors (p = 0.004). ALDH1A1+ tumors presented higher CD3+ (p = 0.008), CD4+ (p = 0.005), CD8+ (p = 0.003) and CD20+ (p = 0.006) TILs. ALDH1A1+ (p = 0.018), PD-L1+ (p = 0.004) and HTILs (p < 0.001) were related to smaller tumors. ALDH1A1+ was related to pathologic complete response (pCR) (p = 0.048). At the end of the follow-up (54.4 [38.3−87.6] months), 47 patients (62.7%) remained disease-free, and 20 (26.7%) had died. HTILs were related to improved disease-free survival (p = 0.027). ALDH1A1+ was related to PD-L1+ and HITLs, that might be related to higher pCR rates with neoadjuvant therapy.

Instantaneous wave-free ratio for guiding treatment of nonculprit lesions in patients with acute coronary syndrome: A retrospective study.

BACKGROUND: The aim of this study was to analyze the feasibility of a physiological coronary evaluation with the instantaneous wave-free ratio (iFR) of nonculprit lesions in patients with acute coronary syndrome (ACS) successfully revascularized. METHODS: A multicenter registry including patients of four high-volume PCI centers with ACS and underwent successful revascularization of the culprit vessel and had other nonculprit lesions that were physiologically evaluated with the iFR between January 2017 and December 2019. The primary endpoint was a composite of cardiac death, nonfatal myocardial infarction, probable or definitive stent thrombosis and new revascularization (MACEs). RESULTS: A total of 356 patients with 472 nonculprit lesions were included. The mean age was 66 ± 11 years. The clinical presentation was ACS without persistent ST-segment elevation (NSTE-ACS) in 235 patients (66%) and ST-segment elevation myocardial infarction (STEMI) in 121 patients (34%). After a median follow-up period of 21 (14-30) months, the primary endpoint occurred in 32 patients (9%). There were no differences in outcomes regarding clinical presentation (NSTEMI vs. NSTE-ACS, 9.1 vs. 8.9%, padj  = 0.570) or iFR induced treatment strategy (patients with all lesions revascularized vs. patients with at least one lesion with an iFR > 0.89 deferred for revascularization, 10.5 vs. 8.4%, padj  = 0.476). CONCLUSIONS: The use of the iFR to guide percutaneous coronary intervention decision making in nonculprit lesions seems to be feasible, with an acceptable percentage of MACEs at the mid-term follow-up. Patients with deferred revascularization of lesions without physiological significance and patients undergoing complete revascularization had a similar risk of MACEs.

QT Interval Monitoring with Handheld Heart Rhythm ECG Device in COVID-19 Patients.

Background: QTc prolongation is an adverse effect of COVID-19 therapies. The use of a handheld device in this scenario has not been addressed. Objectives: To evaluate the feasibility of QTc monitoring with a smart device in COVID-19 patients receiving QTc-interfering therapies. Methods: Prospective study of consecutive COVID-19 patients treated with hydroxychloroquine ± azithromycin ± lopinavir-ritonavir. ECG monitoring was performed with 12-lead ECG or with KardiaMobile-6L. Both registries were also sequentially obtained in a cohort of healthy patients. We evaluated differences in QTc in COVID-19 patients between three different monitoring strategies: 12-lead ECG at baseline and follow-up (A), 12-lead ECG at baseline and follow-up with the smart device (B), and fully monitored with handheld 6-lead ECG (group C). Time needed to obtain an ECG registry was also documented. Results: One hundred and eighty-two COVID-19 patients were included (A: 119(65.4%); B: 50(27.5%); C: 13(7.1%). QTc peak during hospitalization did significantly increase in all groups. No differences were observed between the three monitoring strategies in QTc prolongation (p = 0.864). In the control group, all but one ECG registry with the smart device allowed QTc measurement and mean QTc did not differ between both techniques (p = 0.612), displaying a moderate reliability (ICC 0.56 [0.19-0.76]). Time of ECG registry was significantly longer for the 12-lead ECG than for handheld device in both cohorts (p < 0.001). Conclusion: QTc monitoring with KardiaMobile-6L in COVID-19 patients was feasible. Time of ECG registration was significantly lower with the smart device, which may offer an important advantage for prevention of virus dissemination among healthcare providers.

Malignancy following heart transplantation: differences in incidence and prognosis between sexes - a multicenter cohort study.

Male patients are at increased risk for developing malignancy postheart transplantation (HT); however, real incidence and prognosis in both genders remain unknown. The aim of this study was to assess differences in incidence and mortality related to malignancy between genders in a large cohort of HT patients. Incidence and mortality rates were calculated for all tumors, skin cancers (SCs), lymphoma, and nonskin solid cancers (NSSCs) as well as survival since first diagnosis of neoplasia. 5865 patients (81.6% male) were included. Total incidence rates for all tumors, SCs, and NSSCs were lower in females [all tumors: 25.7 vs. 44.8 per 1000 person-years; rate ratio (RR) 0.68, (0.60-0.78), P < 0.001]. Mortality rates were also lower in females for all tumors [94.0 (77.3-114.3) vs. 129.6 (120.9-138.9) per 1000 person-years; RR 0.76, (0.62-0.94), P = 0.01] and for NSSCs [125.0 (95.2-164.0) vs 234.7 (214.0-257.5) per 1000 person-years; RR 0.60 (0.44-0.80), P = 0.001], albeit not for SCs or lymphoma. Female sex was associated with a better survival after diagnosis of malignancy [log-rank p test = 0.0037; HR 0.74 (0.60-0.91), P = 0.004]. In conclusion, incidence of malignancies post-HT is higher in males than in females, especially for SCs and NSSCs. Prognosis after cancer diagnosis is also worse in males.

Effect of hydroxychloroquine, azithromycin and lopinavir/ritonavir on the QT corrected interval in patients with COVID-19.

BACKGROUND: Administration of Hydroxychloroquine and Azithromycin in patients with coronavirus disease 2019 (COVID-19) prolongs QTc corrected interval (QTc). The effect and safety of Lopinavir/Ritonavir in combination with these therapies have seldom been studied. OBJECTIVES: Our aim was to evaluate changes in QTc in patients receiving double (Hydroxychloroquine + Azithromycin) and triple therapy (Hydroxychloroquine + Azithromycin + Lopinavir/Ritonavir) to treat COVID-19. Secondary outcome was the incidence of in-hospital all-cause mortality. METHODS: Patients under treatment with double (DT) and triple therapy (TT) for COVID-19 were consecutively included in this prospective observational study. Serial in-hospital electrocardiograms were performed to measure QTc at baseline and during therapy. RESULTS: 168 patients (±66.2 years old) were included: 32.1% received DT and 67.9% received TT. The mean baseline QTc was 410.33 ms. Patients under DT and TT prolonged QTc interval respect baseline values (p < 0.001), without significant differences between both therapy groups (p = 0.748). Overall, 33 patients (19.6%) had a peak QTc and/or an increase QTc 60 ms from baseline, with a higher prevalence among those with hypokalemia (p = 0.003). All-cause mortality was similar between both strategy groups (p = 0.093) and high risk QTc prolongation was no related to clinical events in this series. CONCLUSIONS: DT and TT prolong the QTc in patients with COVID-19. Addition of Lopinavir/Ritonavir on top of Hydroxychloroquine and Azithromycin did not increase QTc compared to DT.

Clinical Outcomes Following Urgent vs. Elective Percutaneous Mitral Valve Repair.

AIM: To examine procedural and clinical outcomes among patients undergoing percutaneous mitral valve repair (PMVR) within an admission for acute-decompensated heart failure (ADHF). METHODS AND RESULTS: Prospective registry of all consecutive patients with symptomatic mitral regurgitation (MR) grade 3+ or 4+ who underwent PMVR our centre and classified in 2 groups: elective group and urgent PMVR group (within the index admission for ADHF). Echocardiographic, procedural and clinical outcomes were compared between groups. 85 patients (median age 77.0 [67.8-83.4] years, 64.7% male) were treated within the recruitment period. Among them, 17 (20%) underwent urgent MitraClip®. Urgent PMVR were at a higher risk for conventional surgery (p = 0.002) and had worse estimated prognosis according to HF risk scores (p < 0.001). Overall technical success was 100%, without differences between groups. At 30 days, no differences were found in mortality, MR reduction and in NYHA functional improvement between groups. Cumulative estimated survival free from all-cause death was 92.9% (82.4% vs. 95.6%), 89.4% (82.4% vs. 91.1%), 76.3% (82.4 vs. 74.9%) at 6 months, 1-year and 2-years, respectively, with no significant differences between urgent or elective PMVR (p = 0.769). CONCLUSION: MitraClip® implantation can be considered as an urgent therapy during admission for ADHF.

Thrombus in transit through a patent foramen ovale: An unusual cause of cardiac embolism.

A 78-year-old woman with a history of transient ischemic attack was admitted for sudden aphasia. In order to assess the potential cardioembolic source an echocardiogram was performed, which revealed a large mass consistent with a thrombus in transit through a patent foramen ovale. Because of the high risk of systemic embolism, emergent surgical thrombectomy was performed with the intention to discharge the patient safely without any new embolic events. This case report highlights the importance of echocardiography in the evaluation of cardioembolic stroke and the requirement of an emergent approach in case of impending paradoxical embolism.

A case report of arterial and venous thromboembolism in a patient with severe COVID-19 pneumonia.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has spread rapidly worldwide since the outbreak originated in Wuhan, China in December 2019. Cardiovascular complications in patients with severe COVID-19 have been reported and are associated with a worse outcome. Coagulopathy is one of the most common life-threatening complication increasing mortality; however, little evidence is available regarding prevention strategies or its treatment in COVID-19 patients. CASE SUMMARY: We report a case of a 70-year-old woman admitted to hospital with severe COVID-19 bilateral pneumonia who developed severe coagulopathy with multiple both, venous and arterial, embolisms in major vessels such as bilateral pulmonary embolism, acute thrombus in abdominal aorta, and acute thrombotic occlusion of the right iliac common artery. The patient underwent emergent surgical thrombectomy of the right lower limb; in spite of anticoagulant treatment at therapeutic doses, patient presented poor clinical evolution and an infracondylar amputation of right lower limb was made finally. Subsequently, the patient received low molecular weight heparin (LMWH), antibiotics and antiviral therapy improving her renal function and her pneumonia, so she could be discharged safely. DISCUSSION: Prothrombotic coagulopathy due to enhanced acute inflammatory response and diffuse intravascular coagulation has been described in severe critical COVID-19 patients. This state of hypercoagulability is associated with organ dysfunction and mortality and may predispose to both, venous and arterial, thromboembolism. Little data are available regarding the best therapeutic and prevention strategies in this scenario, although thrombosis prophylaxis with LMWH has been associated with a better outcome.

Incidence and prognostic implications of late bleeding events after percutaneous mitral valve repair.

OBJECTIVES: MitraClip is an established therapy for patients with mitral regurgitation (MR) that are considered of high-risk or inoperable. However, late bleeding events (BE) after hospital discharge and their impact on prognosis in this cohort of patients have been poorly investigated. Our purpose is to address the incidence, related factors and clinical implications of BE after hospital discharge in patients treated with MitraClip. METHODS: Prospective registry of all consecutive patients (n = 80) who underwent MitraClip implantation in our Institution between June 2014 and December 2017. BE were defined according to MVARC definitions. A combined clinical end-point including admission for heart failure (HF) and all-cause mortality was established to analyze prognostic implications of BE. RESULTS: During a median follow up of 523.5 days, 41 BE were reported in 21 patients. Atrial fibrillation (AF, HR 4.54, CI95% 1.20-17.10) and combined antithrombotic therapy at discharge (HR 3.52, CI95% 1.03-11.34) were independently associated with BE. In the study period, 15 (18.8%) patients died, 20 (25%) were admitted for HF and 29 (36.3%) presented the combined end-point. After multivariable adjustment BE remained independently associated with an adverse outcome (HR 3.80, CI 95% 1.66-8.72). In the subgroup of patients with AF, HAS-BLED score was higher among subjects with BE (3.1 ±â€¯1.3 vs 2.1 ±â€¯0.9, p = 0.003). HAS-BLED score had a significant discrimination power for the occurrence BE (AUC: 0.677 [0.507-0.848]) in this subgroup. CONCLUSIONS: BE are common after MitraClip and are associated with an impaired outcome. Strategies to reduce bleeding events are paramount in this cohort of patients.