Sacubitril/valsartan for cardioprotection in breast cancer (MAINSTREAM): design and rationale of the randomized trial.

AIMS: In recent years, survival in patients with breast cancer has increased. Despite the improvement in outcomes of those patients, the risk of treatment-related cardiotoxicity remains high, and its presence has been associated with a higher risk of treatment termination and thus lower therapeutic efficacy. Prior trials demonstrated that a preventive initiation of heart failure drugs, including the renin-angiotensin-aldosterone inhibitors, might reduce the risk of treatment-related cardiotoxicity. However, to date, no study investigated the efficacy of sacubitril/valsartan, a novel antineurohormonal drug shown to be superior to the previous therapies, in the prevention of cardiotoxicity in patients with early-stage breast cancer, which is the aim of the trial. METHODS AND RESULTS: MAINSTREAM is a randomized, placebo-controlled, double-blind, multicentre, clinical trial. After the run-in period, a total of 480 patients with early breast cancer undergoing treatment with anthracyclines and/or anti-human epidermal growth factor receptor 2 drugs will be randomized to the highest tolerated dose of sacubitril/valsartan, being preferably 97/103 mg twice daily or placebo in 1:1 ratio. The patients will be monitored, including routine transthoracic echocardiography (TTE) and laboratory biomarker monitoring, for 24 months. The primary endpoint of the trial will be the occurrence of a decrease in left ventricular ejection fraction by ≥5% in TTE within 24 months. The key secondary endpoints will be the composite endpoint of death from any cause or hospitalization for heart failure, as well as other imaging, laboratory, and clinical outcomes, including the occurrence of the cancer therapy-related cardiac dysfunction resulting in the necessity to initiate treatment. The first patients are expected to be recruited in the coming months, and the estimated completion of the study and publication of the results are expected in December 2027, pending recruitment. CONCLUSIONS: The MAINSTREAM trial will determine the efficacy and safety of treatment with sacubitril/valsartan as a prevention of cardiotoxicity in patients with early breast cancer (ClinicalTrials.gov number: NCT05465031).

Post-COVID­19 complications in hospitalized and nonhospitalized patients: the Silesian database of COVID­19 complications (SILCOV­19).

INTRODUCTION: Due to the extent of the pandemic, high prevalence and severity of complications in the early post­recovery period are expected. OBJECTIVES: This study aimed to compare the scope of early post-COVID­19 complications in patients who had the disease and were or were not hospitalized. PATIENTS AND METHODS: This was a prospective, observational, registry­based cohort study conducted at a tertiary cardiovascular hospital in Silesia, Poland. Interdisciplinary diagnostics, including cardiovascular, pneumatological, respiratory, neurological, and psychiatric tests, was performed during the study visit. All patients completed the study. Two­hundred unselected, adult, white men and women with the symptoms of acute COVID­19 were included, of which 86 patients had the disease but did not require hospitalization. RESULTS: The median (interquartile range) time from symptom onset to the study visit was 107 (87-117) and 105 (79-127) days in nonhospitalized and hospitalized patients, respectively. Lung lesions on high­resolution computed tomography were found in 10 (8.8%) and 33 (39.3%) of nonhospitalized and hospitalized patients, respectively (P <0.01); no lesions were visualized on chest X­ray images. Elevated platelet distribution width was found in more than 70% of the patients in both groups. More than half of the patients had insomnia, regardless of the hospitalization status. CONCLUSIONS: The abnormal platelet parameters, functional and radiological findings in the lungs, and insomnia were the most frequent short­term COVID­19 complications in hospitalized and nonhospitalized patients. Considering the number of patients who have had COVID­19 worldwide, a high burden of the post-COVID­19 complications might be expected.

Temporary Trends Concerning the Extent and Efficacy of Atrial Fibrillation Ablation Using Radiofrequency Energy in a Polish Single-Center Experience.

Background and Objectives: Atrial fibrillation (AF) is the most common supraventricular arrhythmia. Currently, catheter ablation is a preferred treatment strategy. The main objective of our study was a temporary trends analysis of patients' data undergoing a single AF ablation procedure using radiofrequency energy (RF). The efficacy of the procedure underwent assessment during a 12-month follow-up. Materials and Methods: We analyzed 585 consecutive patients with symptomatic, recurrent, and drug-refractory AF hospitalized in our department between 2013 and 2018 who underwent RF ablation supported by a 3D electroanatomical system. The baseline characteristics, periprocedural parameters, and efficacy of the procedure at 6-, 9- and 12-month follow-ups were analyzed over the years. Results: The number of patients undergoing ablation increased. Patients with paroxysmal AF predominated (71.5%). However, the number of patients with the persistent type of arrhythmia increased over the years. The percentage of patients with chronic heart failure (CHF) increased to 27.5% in 2018, and patients presented with increasingly larger left atria (LA). In all patients, circumferential pulmonary vein isolation was performed. The percentage of patients who underwent arrhythmogenic substrate modification and cavotricuspid isthmus ablation increased. Over the years, the efficacy of a single procedure at the 12-month follow-up remained without significant differences between the years (72.0%, 69.6%, 75.5%, 74.8%, 71.7%, 71.7%). Conclusions: The rate of patients with CHF and advanced LA disease undergoing more extensive ablation increased over the years. The efficacy of a single procedure remained without significant differences between the years.

Long-term outcomes in patients after left atrial appendage occlusion: The results from the LAAO SILESIA registry.

BACKGROUND: The benefits of oral anticoagulation (OAC) therapy are undeniable. However, such treatment is contraindicated in 2%-10% of patients. According to the latest guidelines, percutaneous left atrial appendage occlusion (LAAO) may be considered in stroke prevention. AIMS: We analyzed the data of patients from the Polish population, who had undergone LAAO procedures in the Silesian Province based on limited reports. METHODS: The data from the SILCARD database of all patients who underwent LAAO between 2006 and 2019, and the data from the databases of the centers performing the procedures in the Silesian Province were included in the LAAO SILESIA registry. We analyzed the efficacy and safety of the procedure and its relationship with the occurrence of stroke and bleeding in the post-hospital follow-up. RESULTS: We analyzed 649 patients with the mean values of CHA2DS2-VASc and HAS-BLED scores of 4.1 and 3.2, respectively. The predominant indication for LAAO was a history of bleeding during OAC. The most frequent in-hospital major adverse cardiac events were anemia, which required blood transfusion (5.5%), and pericardial effusion, which was treated either conservatively (0.9%) or interventionally (1.2%). During hospitalization, stroke was detected in 4 patients and three patients died of any cause. LAAO reduced the annual risk of stroke by 84% and the annual risk of bleeding by 27%. CONCLUSIONS: Based on a "real-life" cohort of patients from the Silesian Province, we concluded that LAAO is related to low in-hospital major cardiovascular adverse events. In the long-term follow-up, LAAO reduced the rates of stroke and bleeding.

One-Year Outcome of Glycoprotein IIb/IIIa Inhibitor Therapy in Patients with Myocardial Infarction-Related Cardiogenic Shock.

BACKGROUND: We aimed to evaluate the effect of intravenous glycoprotein IIb/IIIa receptor inhibitors (GPIs) on in-hospital survival and mortality during and at the 1-year follow-up in patients undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) complicated by cardiogenic shock (CS), who were included in the Polish Registry of Acute Coronary Syndromes (PL-ACS). METHODS: From 2003 to 2019, 466,566 MI patients were included in the PL-ACS registry. A total of 10,193 patients with CS received PCI on admission. Among them, GPIs were used in 3934 patients. RESULTS: The patients treated with GPIs were younger, had lower systolic blood pressure on admission, required inotropes and intra-aortic balloon pump (IABP) support more frequently, and showed a lower efficacy of coronary angioplasty. In both groups, the same rates of in-hospital adverse events were observed. A lower mortality rate was reported in the group treated with GPIs 12 months after admission (54.9% vs. 57.9%, p = 0.002). Therapy with GPI was an independent factor reducing the risk of mortality in the 12-month follow-up. CONCLUSIONS: The addition of GPIs to the standard pharmacotherapy combined with PCI in patients with MI and CS on admission reduced the risk of death in the 12-month follow-up period without increasing in-hospital adverse event rates.

De novo and pre-existing atrial fibrillation in acute coronary syndromes: impact on prognosis and cardiovascular events in long-term follow-up.

AIMS: The aim of the study was to compare in-hospital and long-term prognosis in patients with acute coronary syndromes (ACS) and de novo vs. pre-existing atrial fibrillation (AF). Atrial fibrillation increases the risk of serious adverse events including death in patients with ACS. However, it is unclear whether de novo and pre-existing AF portend a different risk. METHODS AND RESULTS: We analysed the incidence, clinical characteristics, and in-hospital and long-term outcomes in patients with AF and ACS based on combined data from Polish Registry of Acute Coronary Syndrome (PL-ACS) (n = 581 843) and SILICARD (n = 852 063) databases. Atrial fibrillation at admission was diagnosed in of 6.16% patients [de novo: 1129 (2.46%); pre-existing: 1691 (3.7%)]. Groups were compared (N = 1023 vs. 1023) after matching for relevant clinical factors. De novo and pre-existing AF differed in in-hospital diuretic (52% vs. 58%; P = 0.008) and aldosterone inhibitor (27.5% vs. 32.5%; P = 0.02) use, Thrombolysis In Myocardial Infarction (TIMI) flow before percutaneous coronary intervention (P = 0.016), and diuretic (52.1% vs. 58%; P = 0.008) and oral anticoagulant (27.5% vs. 32.5%; P = 0.018) use at discharge. In-hospital mortality in the de novo AF group was significantly higher (13.1% vs. 8.31%; P = 0.0005). Post-discharge 12-month survival was similar between groups (14.5% vs. 15.3%, P = 0.63). Long-term re-hospitalization due to heart failure (22.7% vs. 17.2%; P < 0.005) and medical contact due to AF (48.4% vs. 26.1%, P < 0.0001) rates were higher in the group with pre-existing AF, without the difference of stroke or myocardial infarction occurrence. CONCLUSION: De novo AF accounts for 40% of all AF cases in ACS patients and is an unfavourable in-hospital prognostic factor. The occurrence of de novo AF during ACS should require special attention and caution in the treatment of these patients.

New hope for patients and challenges for the multidisciplinary arrhythmia team: a hybrid convergent approach for atrial fibrillation treatment.

BACKGROUND: Available data suggest the important role of ablation of the left atrial posterior wall and epicardial myocardial layers in rhythm control therapy in patients with persistent drug­refractory atrial fibrillation (AF). However, endocardial ablation is not always effective in transmural substrate modification. The alternative treatment option is minimally invasive hybrid approach (HABL) combining the strengths of surgical and catheter ablation. AIM: This study aimed to assess the periprocedural safety as well as acute and long­term outcomes of HABL for AF. METHODS: This is a retrospective single­center study of patients who underwent HABL using the minimally invasive transabdominal approach between July 2009 and January 2020. Demographic in­hospital data and 12­month follow­up results were obtained. The number of hospitalizations, cardioversions, re­ablations, and severe adverse events in a 3­year period before and after HABL were compared using data from the national healthcare provider. RESULTS: In total, 158 patients (mean [SD] age, 51.02 [10.67] years) who underwent HABL were included; 61.4% had persistent AF. There was a 4.4% incidence of periprocedural complications without any fatalities. In 66% of patients, additional endocardial substrate modification was needed, in 52.6% on the posterior wall. In the 12­month follow­up, most patients (78.3%) remained free of arrhythmias. There was a significant reduction in the number of hospitalizations (for AF, 1.65 vs 0.54; or any other cause, 2.56 vs 1.31 per patient), cardioversions, and re­ablations after HABL (all P <0.05). CONCLUSIONS: The hybrid multidisciplinary approach for treatment of AF is a safe and very effective treatment method in long­term follow­up, which reduces healthcare burden. It could be considered as an alternative therapeutic option especially in patients with persistent AF.

Temporal trends in the availability and efficacy of catheter ablation for atrial fibrillation and atrial flutter in a highly populated urban area.

BACKGROUND: Pulmonary vein isolation has become one of the core modalities of the rhythm control strategy in patients with atrial fibrillation (AF). AIMS: The aim of the study was to analyze temporal trends in the availability and efficacy of AF and atrial flutter (AFL) catheter ablation in an urban area of Upper Silesia in Poland. METHODS: The source data were obtained from the SILCARD (Silesian Cardiovascular Database) covering an adult population of 3.8 million. The final study population included patients with diagnosis code I48 referred for catheter ablation between 2006 and 2017. The data included total number of procedures, patient sex, age, comorbidities, number of hospital admissions, and mortality rate. RESULTS: A total of 2745 patients were enrolled. The number of ablated patients increased more than 10­fold (43 in 2006 vs 507 in 2017; P = 0.008) in the follow­up period. The analysis showed an upward trend in the proportion of women (P = 0.02), hypertension prevalence (P = 0.004), and percentage of patients implanted (P = 0.02). A decrease was observed in the percentage of patients with stable angina (P <0.005) and hospitalization length (P <0.005). The all­cause hospital readmissions rate decreased from 55.8% to 25.4% (P <0.005). There were significant reductions in the 12­month all­cause mortality (2.3% in 2006 vs 0.2% in 2017; P <0.005), stroke (2.3% in 2006 vs 0.2% in 2017; P = 0.047), and myocardial infarction rates (2.3% in 2006 vs 0.4% in 2017; P = 0.03). CONCLUSIONS: A considerable increase in the availability and efficacy of AF / AFL ablations was documented over the 12­year follow­up period.

The influence of ablation power reduction associated with oesophagus location on pulmonary vein isolation results in patients with paroxysmal atrial fibrillation: six-month follow-up.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) could be associated with a thermal oesophageal (EO) injury. To avoid this complication intraluminal EO temperature monitoring and ablation power reduction at the areas with excessive heating could be used. However, the reduced energy could limit the ablation lesion depth, without creation of lasting transmural scar and influence on long-term ablation results. AIM: The primary goal was to evaluate the homogeneity of forced ablation power reduction due to excessive EO heating in different parts of the left atrium. The secondary goal was to assess the influence of power reduction in different EO locations on long-term AF recurrence. METHODS: We examined retrospectively 109 consecutive patients with symptomatic, medically refractory paroxysmal AF, who underwent pulmonary vein isolation using radiofrequency ablation. In 40.4% of the patients the EO course was central (group B) left atrium posterior wall, in 31.2% it was left sided (group A), and in 28.4% it was right sided (group C). RESULTS: The maximal measured temperature (41.0 ± 1.0 vs. 39.2 ± 1.5 vs. 40.6 ± 0.7°C) and forced ablation power (15.9 ± 5.6 vs. 23.5 ± 6.1 vs. 17.4 ± 5.7 W) differed significantly according to the EO course (A, B, C, respectively). In six-month follow-up 76.15% of patients were free of arrhythmias. There was no statistically significant difference between groups (A-C) regarding the AF recurrence rate: 32.4% vs. 20.5% vs. 19.4% (p = 0.37). CONCLUSIONS: The maximal intraluminal EO temperatures and the necessary level of power reduction during AF ablation are inhomogeneous in different parts of the left atrium, but they are not associated with different six-month follow-up results.

Clinical and laboratory determinants of low serum level of 25-hydroxyvitamin D during escalation of pharmacotherapy in heart failure patients.

INTRODUCTION: The activation of the renin-angiotensin-aldosterone (RAA) system is a main element of the pathophysiology of chronic heart failure (CHF), determining its symptoms and prognosis. Vitamin D is an RAA inhibitor, and its deficiency frequently accompanies CHF. The factors determining the concentration of 25-hydroxyvitamin D [25(OH)D] in CHF are not well understood, although an association has been suggested between the deficiency and the advancement of CHF. Also unknown is the influence of therapeutic escalation using recommended agents on the serum level of 25(OH)D. The aim of this study was to examine the incidence of abnormal 25(OH)D concentrations in CHF patients and to establish the clinical and laboratory determinants of low activity of this metabolite. MATERIAL AND METHODS: The retrospective analysis included the data of 412 CHF patients not receiving optimal pharmacological treatment who were initially in NYHA (New York Heart Association) class III or IV. Over the period of 3 months the therapy was escalated until reaching maximum tolerated doses or those recommended by the current guidelines. After optimizing the therapy, the incidence of 25(OH)D deficiency (< 30 ng/ml) and insufficiency (< 20 ng/ml) was established, and clinical and laboratory determinants for these abnormal concentrations were analyzed. RESULTS: Normal serum level, insufficiency, and deficiency of 25(OH)D were observed in, respectively, 41.5%, 26.0% and 32.5% of patients. The NYHA class improved by at least 1 class in 63.6% of patients, remained unchanged in 32.8% of patients, and deteriorated in 3.6% of patients. In multivariables analysis, low availability of natural ultraviolet B (UVB) radiation, loss of body mass during the CHF, higher concentrations of phosphates and albumins, and the presence of diabetes increased the risk of 25(OH)D deficiency, while higher concentrations of uric acid reduced this risk. In patients with a positive response to therapy, the concentration of 25(OH)D was borderline significantly higher (p = 0.055), while insufficiency and deficiency were less frequent (p = 0.02) than in patients without a treatment response, but this pertained only to patients with higher exposure to UVB. These differences were not observed in patients with low UVB exposure. CONCLUSIONS: The concentration of 25(OH)D in CHF patients is not associated with the advancement of the disease, but is strongly determined by the potential availability of UVB radiation. A positive response to therapy increases the concentration of 25(OH)D only in the case of high UVB exposure; other determinants of 25(OH)D level include the patient's metabolic profile and the presence of diabetes.