Cardiologia Croatica. 2024;19(7-8)

Josip Lukenda

Luigi Galvani (1737-1798) studied the contractions of the leg muscle of a decapitated frog, becoming the founder of electrophysiology. His work even inspired artists such as Paul Peel (1860-1892), who painted his famous painting “The Young Biologist” in 1891. Galvani’s work was the foundation for the revolutionary inventions of many other scientists, such as Willem Einthoven (1860-1927), the inventor of the electrocardiogram (ECG). The scientist whose name is pronounced daily by almost every cardiologist in the world is Norman Jefferis Holter (1914-1983), who brought together all previous research and merged them with the ideas of Nikola Tesla on the wireless transfer of energy and information. As his most famous invention, the holter ECG monitor is only one derivate of what can be termed Holter’s technology and can be considered the biomedical part of the discipline called telemetry. Today, we use a number of devices that are fundamentally based on Holter’s technology, e.g. implantable loop recorders or pacemaker interrogations. The technique called continuous arterial pressure monitoring is also based on Holter’s technology, and it is an open question whether we can call this method holter blood pressure monitoring. Regardless, the implantable pulmonary artery pressure monitoring device is the result of the fundamental ideas of Holter and Tesla, and, like many other great scientists, Jeff Holter deserves to have his eponym – holter – used in biomedical literature and in the general history of science.

Anton Šmalcelj

Senior cardiologists can recall the evolution of cardiologists’ views on heart failure (HF) pathophysiology and treatment approaches during their professional career. Milton Packer has recently formulated the progress of HF concepts in four stages: 1) the cardiorenal model (1940s through the 1960s), 2) the cardiocirculatory model or hemodynamic hypothesis (1970s and 1980s), 3) the neurohormonal model (from 1990s up to recently), and 4) the recent cellular stress model. The cardiorenal model relied on digitalis and diuretics. Vasodilators and positive inotropes were viewed with hope at the time of the prevalence of the hemodynamic hypothesis, but did not meet expectations. Only the neurohormonal model with renin-angiotensin-aldosterone system inhibitors and beta-blockers as acting drugs provided permanent improvement in substantial clinical outcomes, including death rates. However, those treatments were ineffective in heart failure with preserved ejection fraction (HFpEF), comprising half of all patients with HF. The serendipitous discovery that sodium-glucose cotransporter-2 (SGLT2) inhibitors, first introduced as antidiabetic drugs, have beneficial cardiac effects, led to clinical trials which proved substantial outcome benefits not only in heart failure with reduced ejection fraction but also in HFpEF. As the mystery shrouding the mechanisms of sodium-glucose cotransporter 2 inhibitors actions began to be unraveled, the cellular stress model of HF was introduced. This review is focused on historical and recent HF pathophysiological concepts, along with the drugs associated with them, but non-pharmacological treatments are also addressed. Finally, the prospects for advancements in the understanding and treatment of HF are also discussed.

Dubravko Petrač, Vjekoslav Radeljić, Diana Delić-Brkljačić, Kristijan Đula

Cardiac resynchronization therapy (CRT) has become an important treatment option for patients with heart failure (HF) with impaired left ventricular function and ventricular conduction delay. Atrial fibrillation (AF) is the most common arrhythmia in these patients, and its presence may interfere with CRT due to a loss of atrioventricular synchrony and competition between biventricular (BIV) capture and normally conducted beats. This issue is important because the loss of effective BIV pacing is associated with poorer outcomes. Therapeutic options for AF in patients receiving CRT include rate control, with drugs or atrioventricular junction ablation, or rhythm control, with amiodarone or AF ablation, with the main goal of ensuring a high percentage of BIV pacing. In this review, we explain how AF may interfere with CRT, present negative effects of AF in these circumstances, and discuss the therapeutic options for AF in this specific population with HF.

Fabio Kadum, Ana Petretić, Koraljka Benko, Slavica Kovačić

We present the case of a 55-year-old male patient with subacute myocardial infarction and hemorrhagic pericardial effusion that led to cardiac tamponade. The patient presented with the clinical picture of shock and a medical history of a three-day fever, as well as repeated syncope the night before admission. Coronarography established subacute occlusion of the first marginal branch of the left coronary artery, and percutaneous coronary intervention was performed on the first marginal branch, and pericardiocentesis was performed as well, which resulted in the evacuation of 450 mL of hemorrhagic pericardial effusion. Extensive imaging eliminated rupture of the left ventricular free wall. Laboratory testing did not demonstrate the presence of comorbid immunological or malignant diseases. The patient’s status subsequently remained stable during hospitalization and in the six-month follow-up, and the pericardial effusion is in regression.

Breda Barbič-Žagar, Tina Dular-Meglič, Jana Golob, Alenka Kmecl, Nataša Uranič, Saša Žikić

Trust in the power of knowledge. Reliability in choosing treatment. Loyalty to a mission that prioritizes health above all. These are the values that have been the foundation of Krka for 70 years. Our main purpose is to be a reliable global partner in health for doctors, pharmacists, and patients, while pursuing our mission to develop high-quality, safe, and effective medicines. The importance of the vertically integrated production model has been recently demonstrated. This model allows us to have complete oversight of the entire production process, from the active ingredient to the finished product, ensuring high-quality. Our innovations demonstrate our dedication to the well-being of consumers. In recent years, we have launched several valuable single-pill combinations. These include widely used combinations of antihypertensives, as well as other combinations for which we were pioneers among pharmaceutical producers. Our extensive portfolio of medicines addresses most common diseases, providing healthcare professionals with a variety of treatment options. We are also one of the few generic pharmaceutical companies whose medicines are supported by numerous post-registration clinical studies, demonstrating their effectiveness and safety in clinical practice. For 70 years, we have been committed to the health of current and future generations.

Natalia Pappo, Jure Samardžić, Hrvoje Jurin, Boško Skorić, Maja Čikeš, Davor Miličić

Advanced heart failure (HF) is characterized by refractory symptoms and frequent rehospitalizations despite the optimal medical therapy. The prevalence of end-stage HF is increasing due to the increasing number of patients with risk factors for cardiovascular diseases and the ageing of the population, and it is a great clinical challenge and burden for the healthcare system. The prognosis of the disease is poor, with a one-year mortality rate of 25% to 75%. Given that the optimal medical therapy is of limited effect, advanced therapeutic methods which include heart transplantation and the mechanical circulatory support are being considered in the treatment of such patients. Heart transplantation is the gold standard for the treatment of end-stage HF, but due to the limited number of donor organs and certain contraindications, some patients will not be treated with this method. Short-term devices for mechanical circulatory support can be used in the treatment of cardiogenic shock and acute deterioration as a bridge to decision, recovery, upgrade or heart transplantation. Long-term devices for left ventricular support are implanted as a bridge to heart transplantation or as destination therapy in patients who are permanently ineligible for heart transplantation. The main challenge in the adequate use of heart transplantation is the disproportion between the need and the number of donors, which requires optimal screening of candidates and better rationalisation of resources. Despite advances in the technology of the devices for mechanical circulatory support, their full potential is limited due to the still underdeveloped long-term right ventricular support, the underdeveloped complete intracorporeal system, the cost (availability) and possible adverse events after implantation such as driveline infections, systemic thrombosis or bleeding. Application of advanced methods of treating HF in carefully selected patients is essential for a successful outcome. Delayed referral of such patients to transplant centres further limits therapeutic options. This paper presents the challenges in the treatment of patients with end-stage HF with reference to the disease itself, pharmacotherapy and the use of advanced treatment methods.