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The year 2023 proved to be a productive period with many remarkable scientific papers published from Hungary in the field of heart failure (HF). Our aim with this brief review is to highlight the results of the most prominent landmark randomized clinical trials as well as other relevant influential publications with significant contribution from Hungarian authors. Several clinical trials were published in 2023 with the primary focus on optimizing medical management. Papers described the use of SGLT2-inhibitors in HF in association with renal dysfunction, COVID‑19 infection, and evaluating their economic impact. A comprehensive manuscript analysed the geographic differences in patient characteristics, treatments, and outcomes in the PARADISE-MI trial population. With regards to GLP1-repecotor agonists, the STEP-HFpEF landmark clinical trial reported a favourable effect for semaglutide in patients with HFpEF and obesity. The intermittent administration of levosimendan did not improve post-hospitalization clinical stability in a population with advanced HF. In the field of cardiac resynchronization therapy (CRT), results of the BUDAPEST-CRT Upgrade trial was published in the European Heart Journal. This was the first prospective, randomized controlled trial to demonstrate that CRT upgrade in patients with intermittent or permanent RV pacing and HFrEF reduces morbidity and mortality. Several papers focused on the greater field of cardiomyopathies, including medical therapies, diuretic use, and cardiotoxicity. Finally, it is important to mention that an issue of Cardiologia Hungarica was published that was entirely dedicated to HF.

Cardiac arrhythmias are among the leading causes of morbidity and mortality worldwide. While antiarrhythmic drugs traditionally represent the first-line management strategy, their use is often limited by profound proarrhythmic effects. Several studies, including randomized control trials (RCTs), have demonstrated the antiarrhythmic efficacy of ranolazine, which is registered as an antianginal agent, while also establishing its safety profile. This review compiles clinical evidence investigating the antiarrhythmic properties of ranolazine, focusing primarily on ventricular tachycardia (VT) and atrial fibrillation (AF), as they are common rhythm abnormalities with serious complications. Data from RCTs indicate that ranolazine reduces VT incidence, although this effect is not universal. Therefore, we attempt to better describe the patient population that gains the most benefit from ranolazine due to VT suppression. Additionally, ranolazine is known to enhance the conversion rate of AF to sinus rhythm when combined with other antiarrhythmic drugs such as amiodarone, highlighting its synergistic effect in the atrium without provoking ventricular dysrhythmias. Despite the heterogeneity in the currently available data, ranolazine appears to be an effective and safe option for the management of various arrhythmias.

Cardiovascular diseases (CVDs) are among the leading causes of morbidity and mortality worldwide. Unhealthy dietary habits have clearly been shown to contribute to the development of CVDs. Beyond the primary nutrients, a healthy diet is also rich in plant-derived compounds. Natural polyphenols, found in fruits, vegetables, and red wine, have a clear role in improving cardiovascular health. In this review, we strive to summarize the results of the relevant pre-clinical and clinical trials that focused on some of the most important natural polyphenols, such as resveratrol and relevant flavonoids. In addition, we aim to identify their common sources, biosynthesis, and describe their mechanism of action including their regulatory effect on signal transduction pathways. Finally, we provide scientific evidence regarding the cardiovascular benefits of moderate, long-term red wine consumption.

Background: The role of hypothermia in post-arrest neuroprotection is controversial. Animal studies suggest potential benefits with lower temperatures, but high-fidelity ECPR models evaluating temperatures below 30 °C are lacking. Objectives: To determine whether rapid cooling to 24 °C initiated upon reperfusion reduces brain injury compared to 34 °C in a swine model of ECPR. Methods: Twenty-four female pigs had electrically induced VF and mechanical CPR for 30 min. Animals were cannulated for VA-ECMO and cooled to either 34 °C for 4 h (n = 8), 24 °C for 1 h with rewarming to 34 °C over 3 h (n = 7), or 24 °C for 4 h without rewarming (n = 9). Cooling was initiated upon VA-ECMO reperfusion by circulating ice water through the oxygenator. Brain temperature and cerebral and systemic hemodynamics were continuously monitored. After four hours on VA-ECMO, brain tissue was obtained for examination. Results: Target brain temperature was achieved within 30 min of reperfusion (p = 0.74). Carotid blood flow was higher in the 24 °C without rewarming group throughout the VA-ECMO period compared to 34 °C and 24 °C with rewarming (p

Background Extracorporeal cardiopulmonary resuscitation improves outcomes after out‐of‐hospital cardiac arrest. However, bleeding and thrombosis are common complications. We aimed to describe the incidence and predictors of bleeding and thrombosis and their association with in‐hospital mortality. Methods and Results Consecutive patients presenting with refractory ventricular tachycardia/ventricular fibrillation out‐of‐hospital cardiac arrest between December 2015 and March 2022 who met the criteria for extracorporeal cardiopulmonary resuscitation initiation at our center were included. Major bleeding was defined by the Extracorporeal Life Support Organization's criteria. Adjusted analyses were done to seek out risk factors for bleeding and thrombosis and evaluate their association with mortality. Major bleeding occurred in 135 of 200 patients (67.5%), with traumatic bleeding from cardiopulmonary resuscitation in 73 (36.5%). Baseline demographics and arrest characteristics were similar between groups. In multivariable analysis, decreasing levels of fibrinogen were independently associated with bleeding (adjusted hazard ratio [aHR], 0.98 per every 10 mg/dL rise [95% CI, 0.96–0.99]). Patients who died had a higher rate of bleeds per day (0.21 versus 0.03, P

Abstract Background It is unknown to what degree of sarcopenia related to heart failure (HF) is reversible with resolution of the HF syndrome. We evaluated whether (1) weight loss prior to left ventricular assist device (LVAD) is associated with pre‐operative sarcopenia as quantified on pre‐operative chest CTs and (2) determine the relationship between weight recovery (increase) after LVAD implantation and reduction of NT‐proBNP levels. Methods In a large single‐centre cohort (n = 502), CT measures of sarcopenia (pectoralis muscle mass indexed to body surface area and tissue attenuation) were correlated with pre‐LVAD BMI trend (n = 190). BMI and NT‐proBNP trends before and after LVAD implantation were evaluated (n = 403). Linear effects modelling was performed to test the association between NT‐proBNP and BMI trends. Results A downtrending BMI prior to LVAD was associated with pectoralis muscle tissue attenuation (P

BackgroundPulmonary capillary wedge pressure (PCWP) is often used as a surrogate for left-ventricular end-diastolic pressure in patients (LVEDP) who are on veno-arterial extracorporeal membrane oxygenation (V-A ECMO) support for cardiogenic shock and cardiac arrest. However, the correlation between PCWP and LVEDP is not clear in the setting of V-A ECMO usage. We sought to evaluate this correlation in this case series.MethodsPatients were referred to our cardiac catheterization laboratory for invasive hemodynamic studies to assess their readiness for VA-ECMO decannulation. All patients underwent simultaneous left and right heart catheterization. Using standard techniques, we measured PCWP and LVEDP simultaneously. Continuous variables were reported as medians with interquartile ranges. The correlation between PCWP and LVEDP was evaluated using simple linear regression and reported as R2.ResultsFour patients underwent invasive hemodynamic studies 4 (2.5, 7) days after VA-ECMO cannulation. All four patients had suffered in-hospital cardiac arrest and had been put on VA-ECMO. At the baseline level of VA-ECMO flow of 4.1 (3.8, 4.4) L/min, the median LVEDP and PCWP were 6 (4, 7.5) mmHg and 12 (6.5, 16) mmHg, respectively. At the lowest level of VA-ECMO flow of 1.9 (1.6, 2.0) L/min, the median LVEDP and PCWP was 13.5 (8.5, 16) mmHg and 15 (13, 18) mmHg, respectively. There was a poor correlation between the simultaneously measured PCWP and LVEDP (R2 = 0.03, p = 0.66).ConclusionsThe PCWP may not correlate well with LVEDP in patients treated with VA-ECMO, particularly at high levels of VA-ECMO support.

Abstract Aims Cardiopulmonary stress test (CPX) is routinely performed when evaluating patient candidacy for left ventricular assist device (LVAD) implantation. The predictive value of hypotensive systolic blood pressure (SBP) response during CPX on clinical outcomes is unknown. This study aims to determine the effect of hypotensive SBP response during to clinical outcomes among patients who underwent LVAD implantation. Methods and results This was a retrospective single center study enrolling consecutive patients implanted with a continuous flow LVAD between 2011 and 2022. Hypotensive SBP response was defined as peak exercise SBP below the resting value. Multivariable Cox‐regression analysis was performed to evaluate the relationship between hypotensive SBP response and all‐cause mortality within 30 and 90 days of LVAD implantation. A subgroup analysis was performed for patients implanted with a HeartMate III (HM III) device. Four hundred thirty‐two patients underwent LVAD implantation during the pre‐defined period and 156 with INTERMACS profiles 3–6 met our inclusion criteria. The median age was 63 years (IQR 54–69), and 52% had ischaemic cardiomyopathy. Hypotensive SBP response was present in 35% of patients and was associated with increased 90 day all‐cause mortality (unadjusted HR 9.16, 95% CI 1.98–42; P = 0.0046). Hazard ratio remained significant after adjusting for age, INTERMACS profile, serum creatinine, and total bilirubin. Findings were similar in the HM III subgroup. Conclusions Hypotensive SBP response on pre‐LVAD CPX is associated with increased perioperative and 90 day mortality after LVAD implantation. Additional studies are needed to determine the mechanism of increased mortality observed.

Arrhythmogenic cardiovascular disorders are associated with considerable morbidity and mortality. Whether cardiac conduction disease is caused by genetic defects, procedural perturbations, valvular disease, ischemia, aging, or heart failure, new therapies are warranted. In this issue of the JCI, Goodyer et al. used state-of-the-art technologies to image the cardiac conduction system (CCS) in real time and to deliver targeted therapies to the CCS and its subcomponents. These findings advance the ability to image and treat specific lineages within the adult heart with the potential for broader applications in the treatment of cardiovascular diseases.

Abstract Aims Outflow graft obstruction is a poorly described complication following left ventricular assist device (LVAD) surgery. We sought to define the incidence of LVAD outflow graft obstruction and assess clinical outcomes with a percutaneous treatment strategy. Methods and results From January 2012 to October 2020, 322 patients with LVAD were managed at our institution. Patients with LVAD outflow graft obstruction were identified by cardiac computed tomography with angiography and invasive haemodynamic assessment and were subsequently treated with percutaneous intervention. Poisson regression was used to analyse time‐dependent differences in the incidence of LVAD outflow graft obstruction. Kaplan–Meier analysis was used to estimate survival. Twenty patients (6.2%) developed haemodynamically significant LVAD outflow graft obstruction at a rate of 0.03 events per patient‐year. Outflow graft obstruction presented a median of 33 (26–49) months after surgery. Patients presented with low estimated LVAD pump flow (95%), heart failure (90%), or both (85%), and 59% developed cardiogenic shock prior to intervention. The most common aetiology identified by cardiac computed tomography with angiography was external compression of the outflow graft (78%). On presentation, the median peak gradient in the outflow graft was 78 (64–100) mmHg. Outflow graft stenting was 100% successful with no in‐hospital mortality, and it reduced the peak outflow graft gradient to 10 (2–17) mmHg (P

The steadily rising prevalence of heart failure (HF) and the associated increase in health care expenditures represent a significant burden for patients, caregivers, and society. Ambulatory management of worsening congestion is a complex undertaking that requires diuretic escalation, yet clinical success is often hindered by the progressively declining bioavailability of oral agents. Once beyond a threshold, patients with acute on chronic HF often require hospital admission for intravenous diuresis. A novel, pH neutral formulation of furosemide that is administered by a biphasic drug delivery profile (80 mg total over 5 ​hours) via an automated, on-body infusor was designed to overcome these limitations. Early studies have shown that it has equivalent bioavailability with comparable diuresis and natriuresis to the intravenous formulation, leads to significant decongestion, and improvement in quality of life. It was shown to be safe and is well tolerated by patients. Although there is one ongoing clinical trial, available data have demonstrated the potential to shift hospital-administered, intravenous diuresis to the outpatient setting. Reduction in the need for recurrent hospital admissions would be highly desirable by most patients with chronic HF and would lead to a significant reduction in health care expenditures. In this article, we describe the rationale and evolution of this novel PH neutral formulation of furosemide administered subcutaneously, summarize its pharmacokinetic and pharmacodynamic profiles, and review emerging clinical trials demonstrating its clinical safety, efficacy, and potential to reduce health care expenditures.

It has been long known that blood health heavily influences optimal physiological function. Abnormalities affecting the physical properties of blood have been implicated in the pathogenesis of various disorders, although the exact mechanistic links between hemorheology and clinical disease manifestations remain poorly understood. Often overlooked in current medical practice, perhaps due to the promises offered in the molecular and genetic era, the physical properties of blood which remain a valuable and definitive indicator of circulatory health and disease. Bridging this gap, the current manuscript provides an introduction to hemorheology. It reviews the properties that dictate bulk and microcirculatory flow by systematically dissecting the biomechanics that determine the non-Newtonian behavior of blood. Specifically, the impact of hematocrit, the mechanical properties and tendency of red blood cells to aggregate, and various plasma factors on blood viscosity will be examined. Subsequently, the manner in which the physical properties of blood influence hemodynamics in health and disease is discussed. Special attention is given to disorders such as sickle cell disease, emphasizing the clinical impact of severely abnormal blood rheology. This review expands into concepts that are highly topical; the relation between mechanical stress and intracellular homeostasis is examined through a contemporary cell-signaling lens. Indeed, accumulating evidence demonstrates that nitric oxide is not only transported by erythrocytes, but is locally produced by mechanically-sensitive enzymes, which appears to have intracellular and potentially extracellular effects. Finally, given the importance of shear forces in the developing field of mechanical circulatory support, we review the role of blood rheology in temporary and durable mechanical circulatory support devices, an increasingly utilized method of life support. This review thus provides a comprehensive overview for interested trainees, scientists, and clinicians.

Introduction: The COVID-19 pandemic and consequent social isolation prompted a surge in mental health disorders and substance use in the general population and, therefore, in potential organ donors. We aimed to evaluate if this led to a change in donor characteristics, including the mechanism and circumstance of death, and how this may have affected clinical outcomes following heart transplantation. Methods: We identified all heart donors from the SRTR database between 18 October 2018 and 31 December 2021, excluding those who donated immediately after the US national emergency declaration. Donors were stratified into pre-COVID-19 (Pre-Cov; through 12 March 2020) and post-COVID-19 national emergency declaration cohorts (Post-Cov; 1 August 2020 through 31 December 2021) based on the heart procurement date. Relevant demographics, cause of death, and substance use history were collected in addition to graft cold ischemic time, the incidence of primary graft dysfunction (PGD), and recipient survival at 30 days post-transplant. Results: A total of 10,314 heart donors were identified; 4941 were stratified into the Pre-Cov and 5373 into the Post-Cov cohorts. There was no difference in demographics, but illicit drug use was significantly higher in the Post-Cov group, leading to an increased incidence of death from drug intoxication. Fatal gunshot wounds were also more common. Despite these changes, the incidence of PGD remained similar (p = 0.371), and there was no difference in 30 days recipient survival (p = 0.545). Conclusion: Our findings confirm that COVID-19 had a major impact on mental health and psychosocial life with an associated increase in illicit substance use and fatal intoxication rates in heart transplant donors. These changes did not alter peri-operative mortality following heart transplantation. Future studies are needed to ensure that long-term outcomes remain unaffected.

The rising incidence and recognition of cardiogenic shock has led to an increase in the use of veno-arterial extracorporeal membrane oxygenation (VA-ECMO). As clinical experience with this therapy has increased, there has also been a rapid growth in the body of observational and randomized data describing the clinical and logistical considerations required to institute a VA-ECMO program with successful clinical outcomes. The aim of this review is to summarize this contemporary data in the context of four key themes that pertain to VA-ECMO programs: the principles of patient selection; basic hemodynamic and technical principles underlying VA-ECMO; contraindications to VA-ECMO therapy; and common complications and intensive care considerations that are encountered in the setting of VA-ECMO therapy.

Cardiogenic shock accounts for ~100,000 annual hospital admissions in the United States. Despite improvements in medical management strategies, in-hospital mortality remains unacceptably high. Multiple mechanical circulatory support devices have been developed with the aim to provide hemodynamic support and to improve outcomes in this population. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is the most advanced temporary life support system that is unique in that it provides immediate and complete hemodynamic support as well as concomitant gas exchange. In this review, we discuss the fundamental concepts and hemodynamic aspects of VA-ECMO support in patients with cardiogenic shock of various etiologies. In addition, we review the common indications, contraindications and complications associated with VA-ECMO use.

A 66-year-old male with recent diagnosis of heart failure with reduced ejection fraction was referred to our institution for management of cardiogenic/vasodilatory shock. During his evaluation, he suffered a sudden cardiac arrest from refractory ventricular tachycardia/fibrillation (VT/VF) despite normal electrolytes and no evidence of prior ventricular arrhythmias. He was placed on rescue peripheral veno-arterial extracorporeal membrane oxygenation support (VA-ECMO) for 4 days and was decannulated without end-organ damage. Continued workup revealed Mayo stage IV immunoglobulin light chain (AL) amyloidosis. Unfortunately, he developed acute cerebellar hemorrhage several days later. Autopsy findings were consistent with AL amyloidosis, with extensive cardiac fibrosis and amyloid deposition in the myocardium and vasculature.While the most common cause of cardiac death in patients with amyloidosis is severe bradycardia and pulseless electrical activity, sustained ventricular arrhythmias have been reported. The use of implantable cardioverter defibrillators (ICD) is highly debated in this population given the lack of survival benefit. Our patient also developed refractory VT/VF arrest, and ICD shocks would not have rescued him while causing significant distress. Emergent VA-ECMO cannulation allowed us to make a diagnosis, yet this intervention cannot be routinely recommended given the limited survival of patients with AL amyloidosis.

The direct and indirect adverse effects of SARS-CoV-2 infection on the cardiovascular system, including myocarditis, are of paramount importance. These not only affect the disease course but also determine clinical outcomes and recovery. In this review, the authors aimed at providing an update on the incidence of Coronavirus disease-2019 (COVID-19)-associated myocarditis. Our knowledge and experience relevant to this area continues to evolve rapidly since the beginning of the pandemic. It is crucial for the scientific and medical community to stay abreast of current information. Contrasting early reports, recent data suggest that the overall incidence of SARS-CoV-2-associated myocarditis is relatively low, yet infected individuals are at a substantially increased risk. Therefore, understanding the pathophysiology and diagnostic evaluation, including the use of serum biomarkers and imaging modalities, remain important. This review aims to summarize the most recent data in these areas as they relate to COVID-19-associated myocarditis. Given its increasing relevance, a brief update is included on the proposed mechanisms of myocarditis in COVID-19 vaccine recipients.

Cardiac transplantation requires the careful allocation of a limited number of precious organs. Therefore, it is critical to select candidates that will receive the greatest anticipated medical benefit but will also serve as the best stewards of the organ. Individual transplant teams have established prerequisites pertaining to recreational drug, tobacco, alcohol, and controlled substance use in potential organ recipients and post-transplantation. Legalization of cannabis and implementation of its prescription-based use for the management of patients with chronic conditions have been increasing over the past years. Center requirements regarding abstinence from recreational and medical cannabis use vary due to rapidly changing state regulations, as well as the lack of clinical safety data in this population. This is evident by the results of the multicenter survey presented in this paper. Developing uniform guidelines around cannabis use will be imperative not only for providers but also for patients.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) gained worldwide attention at the end of 2019 when it was identified to cause severe respiratory distress syndrome. While it primarily affects the respiratory system, we now have evidence that it affects multiple organ systems in the human body. Cardiac manifestations may include myocarditis, life threatening arrhythmias, acute coronary syndrome, systolic heart failure, and cardiogenic shock. Myocarditis is increasingly recognized as a complication of Coronavirus-19 (COVID-19) and may result from direct viral injury or from exaggerated host immune response. The diagnosis is established similar to other etiologies, and is based on detailed history, clinical exam, laboratory findings and non-invasive imaging studies. When available, cardiac MRI is the preferred imaging modality. Endomyocardial biopsy may be performed if the diagnosis remains uncertain. Current management is mainly supportive with the potential addition of interventions recommended for severe COVID-19 disease, such as remdesivir, steroids, and convalescent plasma. In the setting of cardiogenic shock and refractory, life-threatening arrhythmias that persist despite medical therapy, advanced mechanical circulatory support devices should be considered. Ultimately, early recognition and aggressive intervention are key factors in reducing morbidity and mortality. Our management strategy is expected to evolve further as we learn more about COVID-19 disease and the associated cardiac complications.

Background Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease.Design and Methods We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA).Results Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates.Conclusions The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.