Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality worldwide, including in Croatia. Since most patients have multiple disorders and diseases caused largely by the same risk factors, and as it is essential to approach each patient as a person with all disorders, today, we are talking about a new paradigm—cardio-renal-metabolic (CKM) syndrome and cardio-renal-metabolic health, which necessarily includes brain health. Elevated systolic blood pressure, LDL cholesterol, smoking, obesity, diabetes, impaired renal function or chronic kidney disease, which all stem from insufficient physical activity, an unhealthy diet with excessive intake of table salt, and air pollution, are the leading causes of overall morbidity and mortality from CKM diseases, especially mortality from CVD. Experts from various fields key to CKM health have written this document with the aim of integrating it as part of the national plan for the prevention of chronic non-communicable diseases with a focus on CVD, which should become mandatory and be based on the existing guidelines of professional societies.

This study was designed to examine the association between myocardial concentrations of the trace elements Cu, Fe, Mn, Mo, and Zn and the expression of mitochondrial unfolded protein response (UPRmt) elements and the age of patients who received heart transplantation or a left-ventricular assist device (ageHTx/LVAD). Inductively coupled plasma mass spectrometry was used to determine the concentration of Cu, Fe, Mn, Mo, and Zn in the myocardium of control subjects and patients undergoing heart transplantation or left-ventricular assist device (LVAD) implantation. We used ELISA to quantify the expression of UPRmt proteins and 4-Hydroxynonenal (4-HNE), which served as a marker of oxidative-stress-induced lipid peroxidation. Concentrations of Cu, Mn, Mo, and Zn were similar in the control and heart failure (HF) myocardium, while Fe showed a significant decrease in the HF group compared to the control. A higher cumulative concentration of Fe and Zn in the myocardium was associated with reduced age_HTx/LVAD, which was not observed for other combinations of trace elements or their individual effects. The trace elements Cu, Mn, and Zn showed positive correlations with several UPRmt proteins, while Fe had a negative correlation with UPRmt effector protease YME1L. None of the trace elements correlated with 4-HNE in the myocardium. The concentrations of the trace elements Mn and Zn were significantly higher in the myocardium of patients with dilated cardiomyopathy than in patients with ischemic cardiomyopathy. A higher cumulative concentration of Fe and Zn in the myocardium was associated with a younger age at which patients received heart transplantation or LVAD, potentially suggesting an acceleration of HF. A positive correlation between myocardial Cu, Mn, and Zn and the expression of UPRmt proteins and a negative correlation between myocardial Fe and YME1L expression suggest that these trace elements exerted their actions on the human heart by interacting with the UPRmt. An altered generation of oxidative stress was not an underlying mechanism of the observed changes.

Dietary inorganic nitrate lowers blood pressure (BP) in healthy individuals through improved nitric oxide (NO) bioavailability. However, there is limited evidence examining the long-term effects of dietary nitrate for managing hypertension. We aimed to determine whether the sustained intake of dietary nitrate improved BP and cardiovascular disease (CVD) risk factors in individuals with early-stage hypertension. The Dietary Nitrate (NO₃) on BP and CVD Risk Factors (DINO₃) Trial was a multi-center, double-blinded, parallel, randomized, controlled trial in participants with elevated BP. Participants were supplemented with high-nitrate (HN) (~400 mg nitrate) or low-nitrate (LN) vegetable powder (~50 mg nitrate) on top of their usual diets for 16 weeks. The primary outcome was office systolic BP at 16 weeks. The secondary outcomes were 24 h ambulatory BP, central BP, heart-rate-corrected augmentation index (AIx75), carotid–femoral pulse wave velocity (cf-PWV), lipids, and high-sensitivity C-reactive protein (hs-CRP). Sixty-six participants were randomized at baseline (39M:27F, age: 51.5 ± 10.8 years, BMI:27.9 ± 3.2 kg/m²). In an intention-to-treat analysis, no differences were observed between HN and LN groups in terms of office systolic BP at 16 weeks (3.91 ± 3.52 mmHg, p = 0.27) or secondary outcomes. In this exploratory study, sustained HN vegetable supplementation did not exhibit more favorable vascular effects than LN vegetable supplementation in individuals with elevated BP.

Heart failure (HF) is a common cause of morbimortality with different etiopathogenesis and prognosis between men and women. This review provides a brief overview of gender-based differences in response to pharmacological therapies of heart failure with or without reduced ejection fraction (EF). It focuses on the differences in therapy outcomes with angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs), angiotensin neprilysin inhibitors (ARNI), beta-adrenergic blockers, mineralocorticoid/aldosterone receptor antagonists, diuretics, ivabradine and digoxin. The baseline data originates from randomised controlled trials (RCTs) and large registries. We conclude that current guidelines recommending similar therapeutic approaches for both men and women are appropriate, while additional consideration should be given for different approaches regarding the use of ARBs, ACEi, and digoxin. Based on the available data, the ARBs might be considered a first-line therapy of HR for women instead of ACEi. Moreover, female patients should have stricter digoxin monitoring due to higher sensitivity and increased risk of complications. Finally, women are underrepresented in current clinical trials, and therefore future trials should aim to balance the gender recruitment disparity allowing sub-group analysis and comparisons between genders to guide individualised therapeutic strategies and appropriately targeted preventative steps.

A 44-year-old female patient with chemotherapy-induced cardiomyopathy presented with acute cardiogenic shock requiring ECMO support. Multiple failed weaning trials from temporary mechanical circulatory assistance prompted a transition to staged durable biventricular support. Her course was complicated with recurrent RVAD stoppages. The initial event was treated with pump exchange, while for the subsequent RVAD standstill, we employed a device wash-out and reimplantation strategy. A brief period of circulatory arrest was employed to explore the right-sided cardiac chambers using a single-use bronchoscope.

With notable improvements in long-term survival and hemocompatibility-related events, heart failure (HF) is emerging as a leading cause of death in the contemporary left ventricular assist device (LVAD) population. While prospective randomized controlled trials (RCTs) have not investigated the use of HF therapies in LVAD recipients, observational data suggest benefits of neurohormonal blockers, especially in achieving blood pressure (BP) targets associated with improved outcomes. ENVAD-HF is an investigator-initiated prospective multicenter, randomized, open-label, parallel group, pilot study in HeartMate 3 (HM3) LVAD recipients to evaluate the safety and tolerability and insights on efficacy of sacubitril/valsartan compared to standard of care (SOC) for managing BP. Medically stable LVAD recipients after a recent HM3 implantation or in ambulatory follow-up were eligible for participation and randomized 1:1 to receive sacubitril/valsartan or SOC used for treating BP, both titrated aiming for a mean arterial pressure (MAP) goal 75-90 mmHg over a 12-month follow-up. The primary endpoint, designed to assess the safety and efficacy of sacubitril/valsartan compared to SOC, is a composite of freedom from all-cause death, deterioration in renal function, hyperkalemia or symptomatic hypotension. The occurrence of the primary endpoint will be assessed in the first three months and during the overall duration of the trial (12 months). Other endpoints include clinical and patient-reported outcomes, biomarker and echocardiography assessments during follow-up. ENVAD-HF enrolled 60 patients between February 2021 and March 2024: 17% females, mean age 57±12 years, 67% in ambulatory follow-up, 55% ischemic etiology, 25% receiving an LVAD as destination therapy, with mean baseline MAP 87±7 mmHg and median NTproBNP 2552 (1595-3543] pg/mL. ENVAD-HF is the first prospective RCT of pharmacological therapy for management of BP in stable HM3 LVAD recipients achieving target enrolment. It will provide data on safety, tolerability and insights on efficacy of sacubitril/valsartan versus SOC used for treating BP.