J. Cardiovasc. Dev. Dis., Volume 9, Issue 3 (March 2022) – 26 articles

Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality. Interestingly, male and female patients with CVD exhibit distinct epidemiological and pathophysiological characteristics, implying a potentially important role for primary and secondary sex determination factors in heart development, aging, disease and therapeutic responses. Here, we provide a concise review of the field and discuss current gaps in knowledge as a step towards elucidating the “sex determination–heart axis”. We specifically focus on cardiovascular manifestations of abnormal sex determination in humans, such as in Turner and Klinefelter syndromes, as well as on the differences in cardiac regenerative potential between species with plastic and non-plastic sexual phenotypes. Sex-biased cardiac repair mechanisms are also discussed with a focus on the role of the steroid hormone 17β-estradiol. Understanding the “sex determination–heart axis” may offer new therapeutic possibilities for enhanced cardiac regeneration and/or repair post-injury. Full article

Maternal mortality in the United States has been on the rise. Every year, about 700 women die from pregnancy-related complications. Cardiovascular disease (CVD) accounts for a large majority of pregnancy-related deaths driven by the lack of recognition and delays in diagnosis due to the overlap of normal pregnancy symptoms with those of CVD. Risk factors for CVD including race, advanced maternal age, hypertension, diabetes, obesity, socioeconomic status, and geographic region play an important role in CVD-related deaths. Several risk assessment models are available to stratify women with a known diagnosis of CVD. However, most women who die from CVD during pregnancy or the postpartum period do not have a prior diagnosis of CVD, and cardiomyopathy is an important contributor. The California Maternal Quality Care Collaborative (CMQCC) developed an algorithm to screen all pregnant and postpartum women to allow stratification into low or high risk for CVD. The algorithm has been validated in diverse patient populations. We propose universal CVD screening for all women in the antepartum and postpartum period to identify women at risk and to provide education and awareness for both patients and healthcare providers. This screening tool would work to reduce the increasing rates of severe maternal mortality and morbidity while having a significant impact on healthcare costs in the United States. Full article

Introduction: Currently, numerous ablation techniques are available for atrial fibrillation (AF), in addition to manual radio frequency ablation. The aim of this prospective, non-randomized concurrent controlled trial was to compare the mid-term efficacy and procedural outcomes of persistent AF (PerAF) using cryoballoon (CB) and robotic magnetic navigation (RMN). Methods: Two hundred PerAF patients were assigned, in a 1:1 ratio, to undergo catheter ablation using RMN (RMN group) or CB (CB group). The primary endpoint was freedom from AF recurrence following a 3-month period after the index ablation. The secondary endpoint was peri-procedural outcomes, including the total procedure time, left atrial procedure time, fluoroscopy time, and fluoroscopy dose. The Two-step cluster analysis was used to determine the efficacy of RMN and CB between the different groups. The Cox proportional hazard model and restricted cubic spline were used to determine predictors for AF recurrence. Results: At the mean follow-up of 28.1 ± 9.7 months, the primary endpoint was achieved in 71 PerAF patients in the RMN group and in 62 PerAF patients in the CB group (71% vs. 62%, p = 0.158). Compared with CB, RMN-guided ablation led to a longer procedure time (p < 0.001), but with less radiation (p < 0.001). Cluster analysis returned two clusters of patients and RMN was favorable for one cluster (p = 0.037), in which more patients presented with diabetes mellitus and smaller left atria. Conclusions: For patients with PerAF, CB is generally equivalent to RMN-guided ablation with regard to overall efficacy. RMN-guided ablation could be favorable in specific patient populations presenting with diabetes mellitus and smaller left atria. Full article

More than half of patients with heart failure have a preserved ejection fraction (HFpEF). The prevalence of HFpEF has been increasing worldwide and is expected to increase further, making it an important health-care problem. The diagnosis of HFpEF is straightforward in the presence of obvious objective signs of congestion; however, it is challenging in patients presenting with a low degree of congestion because abnormal elevation in intracardiac pressures may occur only during physiological stress conditions, such as during exercise. On the basis of this hemodynamic background, current consensus guidelines have emphasized the importance of exercise stress testing to reveal abnormalities during exercise, and exercise stress echocardiography (i.e., diastolic stress echocardiography) may be used as an initial diagnostic approach to HFpEF owing to its noninvasive nature and wide availability. However, evidence supporting the use of this method remains limited and many knowledge gaps exist with respect to diastolic stress echocardiography. This review summarizes the current understanding of the use of diastolic stress echocardiography in the diagnostic evaluation of HFpEF and discusses its strengths and limitations to encourage future studies on this subject. Full article

Background and aims: Auscultation is a cheap and fundamental technique for detecting cardiovascular disease effectively. Doctors’ abilities in auscultation are varied. Sometimes, there may be cases of misdiagnosis, even when auscultation is performed by an experienced doctor. Hence, it is necessary to propose accurate computational tools to assist auscultation, especially in developing countries. Artificial intelligence technology can be an efficient diagnostic tool for detecting cardiovascular disease. This work proposed an automatic multiple classification method for cardiovascular disease detection by heart sound signals. Methods and results: In this work, a 1D heart sound signal is translated into its corresponding 3D spectrogram using continuous wavelet transform (CWT). In total, six classes of heart sound data are used in this experiment. We combine an open database (including five classes of heart sound data: aortic stenosis, mitral regurgitation, mitral stenosis, mitral valve prolapse and normal) with one class (pulmonary hypertension) of heart sound data collected by ourselves to perform the experiment. To make the method robust in a noisy environment, the background deformation technique is used before training. Then, 10 transfer learning networks (GoogleNet, SqueezeNet, DarkNet19, MobileNetv2, Inception-ResNetv2, DenseNet201, Inceptionv3, ResNet101, NasNet-Large, and Xception) are used for comparison. Furthermore, other models (LSTM and CNN) are also compared with our proposed algorithm. The experimental results show that four transfer learning networks (ResNet101, DenseNet201, DarkNet19 and GoogleNet) outperformed their peer models with an accuracy of 0.98 to detect the multiple heart diseases. The performances have been validated both in the original heart sound and the augmented heart sound using 10-fold cross validation. The results of these 10 folds are reported in this research. Conclusions: Our method obtained high classification accuracy even under a noisy background, which suggests that the proposed classification method could be used in auxiliary diagnosis for cardiovascular diseases. Full article

Purpose: Low-intensity resistance exercise with moderate blood-flow restriction (LIRE-BFR) is a new trending form of exercises worldwide. The purpose of this study was to compare the acute effect of a single bout of traditional resistance exercise (TRE) and LIRE-BFR on arterial stiffness in older people with slow gait speeds. Methods: This was a randomized, controlled clinical study. Seventeen older adults (3 men; 14 women; 82 ± 5 years old) completed a session of TRE (n = 7) or LIRE-BFR (n = 10). At baseline and after 60 min post-exercise, participants were subject to blood pressure measurement, heart rate measurements and a determination of arterial stiffness parameters. Results: There was no significant difference between the TRE and LIRE-BFR group at baseline. Pulse-wave velocity increased in both groups (p < 0.05) post-exercise with no between-group differences. Both exercise modalities did not produce any adverse events. The increase in systolic blood pressure, pulse pressure, augmentation pressure and pulse wave velocity (all p > 0.05) were similar after both TRE and LIRE-BFR. Conclusion: TRE and LIRE-BFR had similar responses regarding hemodynamic parameters and pulse-wave velocity in older people with slow gait speed. Long-term studies should assess the cardiovascular risk and safety of LIRE-BFR training in this population. Full article

Clinical presentation is one of the factors that can influence how quickly a patient with an acute coronary syndrome is treated, particularly if it is atypical. The purposes of this study are to explore gender-related differences in patients presenting with non-ST elevation acute coronary syndromes (NSTEACS) from the perspective of a series of common risk factors as well as treatment strategies and to evaluate the prevalence of atypical clinical presentation of NSTEACS in the study group. In addition, we explored the differences between the two entities that define NSTEACS: unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI). We conducted a retrospective study by reviewing discharge documents of patients admitted in the cardiology department of the Clinical Rehabilitation Hospital in Cluj-Napoca with NSTEACS between January 2014 and December 2015. We retrieved demographic data, clinical presentation and history, laboratory tests, and coronary angiography records as well as the implemented treatment strategies. Women in the study group were more frequently hypertensive than men (89.5% vs. 75.4%; p = 0.043), had a higher mean serum HDL cholesterol value (43 vs. 38 mg/dL p = 0.022), were more frequently diagnosed with microvascular coronary heart disease (32% vs. 9.8%, p = 0.036), and were more often treated conservatively (49.1% vs. 30.8%, p = 0.038), while men were significantly more prone to smoking than women (30.8% vs. 14%, p = 0.028) and had higher mean serum creatinine (1.2 vs. 0.8 mg/dL; p = 0.022) and uric acid values (6.9 vs. 6.2 mg/dL; p = 0.048). Out of the 122 included patients, 109 had documented information regarding symptoms. The prevalence of atypical presentation was 4.6% (95% CI 0.7–8.5%). In our study group, patients with UA had a more frequent history of cardiovascular ischemic diseases (77.4% vs. 56.7%, p = 0.015), the mean value for BUN was higher in NSTEMI patients compared to patients with UA (47 vs. 39 mg/dL, p = 0.038) and NSTEMI patients more frequently received interventional treatment compared to patients with UA (60% vs. 41.9%; p = 0.046). Full article

Coronary endarterectomy (CE) emerged as a necessity to achieve complete surgical myocardial revascularization in patients with diffusely diseased coronary arteries and it also serves as aid to coronary bypass grafting (CABG). The safety and postoperative prognosis of this procedure are still matters of debate. There are no clear preoperative indications, a standard technique has not yet been established as gold standard and the postoperative management differs depending on each institution. CE of the left anterior descending artery (LAD) is technically challenging and potentially hazardous with high risk of postoperative myocardial infarction. In this article, we describe the open technique for CE of the LAD with its specific details, which we believe could be the safest and the best reproductible option. To better understand the profile of a patient requiring such a procedure we present the case of a 73-years old male with diffused coronary artery disease (CAD) and a short review of literature. Full article

Coronary artery disease (CAD) is a common chronic condition in the elderly. However, the earlier CAD begins, the stronger its impact on lifestyle and costs of health and social care. The present study analyzes clinical and angiographic features and the outcome of very young patients undergoing coronary angiography due to suspected CAD, including a nested case-control study of ≤40-year-old patients referred for coronary angiography. Patients were divided into two groups: cases with significant angiographic stenosis, and controls with non-significant stenosis. Of the 19,321 coronary angiographies performed in our center in a period of 10 years, 504 (2.6%) were in patients ≤40 years. The most common cardiovascular risk factors for significant CAD were smoking (OR 2.96; 95% CI 1.65–5.37), dyslipidemia (OR 2.18; 95% CI 1.27–3.82), and family history of CAD (OR 1.95; 95% CI 1.05–3.75). The incidence of major adverse cardiovascular events (MACE) at follow-up was significantly higher in the cases compared to controls (HR 2.71; 95% CI 1.44–5.11). Three conventional coronary risk factors were directly related to the early signs of CAD. MACE in the long-term follow-up is associated to dyslipidaemia and hypertriglyceridemia. Focusing efforts for the adequate control of CAD in young patients is a priority given the high socio-medical cost that this disease entails to society. Full article

We reported the novel use of a taurolidine-containing antimicrobial solution in the successful salvage of a partially exposed and polymicrobially infected cardiac implantable electronic device pulse generator in a frail patient unfit for lead extraction. The old, salvaged device was entirely internalized, and there were no signs of recurrent infection at 9 months follow-up. Full article

The information on heart transplantation (HT) in patients with Friedreich’s Ataxia (FA) is scarce, and the few published case reports are limited to young patients with mild neurological manifestations. We present the case of a 58-year-old patient with advanced FA (Scale for the Assessment and Rating of Ataxia [SARA] score 30/40), wheelchair-bound for the last 16 years and had urinary incontinence, dysarthria, and neurosensorial deafness. The patient was admitted for a refractory arrhythmic storm and had previous hypertrophic cardiomyopathy that evolved to dilated cardiomyopathy with severely reduced left ventricular ejection fraction and recurrent ventricular arrhythmias. A multidisciplinary team discussed the HT option. The patient was aware of the risks and benefits and considered worthy of the intervention, so he was listed for HT. After a successful surgical intervention, the patient had a long postoperative stay in ICU. He required a high dose of vasopressors, underwent hemofiltration for one month, suffered critical illness myopathy, had several respiratory infections and delayed tracheal extubation. Two and a half months after HT and almost five months at the hospital, the patient was successfully discharged. FA patients with severe heart conditions should be carefully evaluated by a multidisciplinary team to decide the candidacy for HT. Full article

The pathophysiology of Takotsubo Syndrome (TTS) is not completely understood and the trigger of sudden cardiac death (SCD) in TTS is not clear either. We therefore sought to find an association between TTS and primary electrical diseases. A total of 148 TTS patients were analyzed between 2003 and 2017 in a bi-centric manner. Additionally, a literature review was performed. The patients were included in an ongoing retrospective cohort database. The coexistence of TTS and primary electrical diseases was confirmed in five cases as the following: catecholaminergic polymorphic ventricular tachycardia (CPVT, 18-year-old female) (n = 1), LQTS 1 (72-year-old female and 65-year-old female) (n = 2), LQTS 2 (17-year-old female) (n = 1), and LQTS in the absence of mutations (22-year-old female). Four patients suffered from malignant tachyarrhythmia and recurrent syncope after TTS. Except for the CPVT patient and one LQTS 1 patient, all other cases underwent subcutaneous ICD implantation. An event recorder of the CPVT patient after starting beta-blocker did not detect arrhythmias. The diagnosis of primary electrical disease was in 80% of cases unmasked on a TTS event. This diagnosis triggered a family clinical and genetic screening confirming the diagnosis of primary electrical disease. A subsequent literature review identified five cases as the following: a congenital atrioventricular block (n = 1), a Jervell and Lange-Nielsen Syndrome (n = 1), and a family LQTS in the absence of a mutation (n = 2), LQTS 2 (n = 1). A primary electrical disease should be suspected in young and old TTS patients with a family history of sudden cardiac death. In suspected cases, e.g., ongoing QT interval prolongation, despite recovery of left ventricular ejection fraction a family screening is recommended. Full article

(1) Background: To determine the prevalence, electrocardiographic characteristics, mapping, and ablation of IVAs arising from the CVS. (2) Methods: Detailed activation and pace mapping of the CVS IVAs was performed before attempted radiofrequency ablation (RFCA). (3) Results: The IVAs originating from the vicinity of the CVS represented approximately 5.27% (164/3113) of all IVAs; 94.51% (155/164) cases were accessed at the earliest identified site and 83.54% (137/164) IVAs were successfully ablated. The main coronary vein group had a relatively short procedure time, short fluoroscopy time, fewer radiofrequency lesions prior to success, and less Swartz sheath support. IVAs originating from the CVS had distinct ECG characteristics: Rs, RS or rS (with s or S) wave in lead V1 indicate the Vas arising from the proximal portion of the anterior interventricular vein (AIV) and summit-CV; Rs (with s or S) wave in leads V5–V6 indicate the Vas arising from the adjacent regions of the distal great cardiac vein 1 (DGCV₁); positive wave (R, Rs or r) In lead I indicate the VAs ori”inat’ng from Summit-CV and posterior wall subgroup (including middle cardiac vein [MCV], posterior lateral vein [PLV], coronary sinus [CS]). Compared with the IVAs originating from the endocardial mitral annulus, a PdW > 45 ms, an IDT > 74 ms, and an MDI > 0.50 indicate a CVS origin of the IVAs. The common peri-procedure complications were CV dissection (6.45%, 10/155), CV rupture (1.29%, 2/155), coronary artery spasm (1.29%, 2/155), coronary artery stenosis (0.65%, 1/155), pericardial effusion (0.65%, 1/155) and tamponade (1.29%, 2/155). Stenosis of coronary arteries was not observed at the adjacent ablation site in the CVS during follow-up. (4) Conclusions: vAs arising from the CVS are not a rare phenomenon. Several ECG and procedure characteristics could help regionalize, map, and ablate the origin of IVAs from different portions of the CVS. RFCA within the CVS was relatively effective and safe. Full article

Background: Left ventricular noncompaction (LVNC) is a distinct cardiomyopathy characterized by the presence of a two-layer myocardium with prominent trabeculation and deep intertrabecular recesses. The diagnosis of LVNC can be challenging because the diagnostic criteria are not uniform. The aim of our study was to evaluate echocardiographic and CMR findings in a group of children with isolated LVNC. Methods: From February 2008 to July 2021, pediatric patients under 18 years of age at the time of diagnosis with echocardiographic evidence of isolated LVNC were prospectively enrolled. The patients underwent echocardiography and contrast-enhanced cardiovascular magnetic resonance (CMR) with late gadolinium enhancement to assess myocardial noncompaction, ventricular size, and function. Results: A total of 34 patients, with a median age of 11.9 years, were recruited. The patients were followed prospectively for a median of 5.1 years. Of the 31 patients who met Jenni’s criteria in echocardiography, CMR was performed on 27 (79%). Further comprehensive analysis was performed in the group of 25 patients who met the echocardiographic and CMR criteria for LVNC. In echocardiography, the median NC/C ratio in systole was 2.60 and in diastole 3.40. In 25 out of 27 children (93%), LVNC was confirmed by CMR, according to Petersen’s criteria, with a median NC/C ratio of 3.27. Conclusions: (1) Echocardiography precisely identifies patients with LVNC. (2) Echocardiography is a good method for monitoring LV systolic function, but CMR is indicated for the precise assessment of LV remodeling and RV size and function, as well as for the detection of myocardial fibrosis. Full article

Recent studies indicate that the disorder of glucose metabolism in myocardial tissue is involved in the development of Takotsubo syndrome (TTS). This study investigated the effects of a high level of glucose on the pathogenesis of TTS, focusing on the electrophysiological mechanisms. Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were treated with toxic concentration of isoprenaline (Iso, 1 mM) and a high level of glucose (22 mM) to mimic the setting of TTS and diabetes mellitus (DM). Iso prolonged action potential duration (APD) through enhancing the late sodium channel current and suppressing the transient outward potassium current (I_to). However, a high level of glucose prevented the APD prolongation and the change in I_to. High-level glucose reduced the expression levels of PI3K/Akt, β1-adrenoceptors, Gs-protein, and PKA, suggesting their involvement in the protective effects of high-level glucose against toxic effects of catecholamine. High glucose level did not influence Iso-induced ROS-generation, suggesting that the protective effects of high-level glucose against Iso did not result from changes in ROS generation. High-level glucose may protect cardiomyocytes from the toxic effects of catecholamine excess through suppressing β1-adrenoceptor-Gs-PKA signaling. DM may reduce the risk for occurrence of arrhythmias due to QT prolongation in TTS patients. Full article

Objectives: Arterial stiffness is widely accepted as an important predictor of cardiovascular disease (CVD) development. While obesity is generally associated with increased CVD risk, there is evidence that overweight patients with existing CVD may have better clinical outcomes than their lean counterparts. Our study sought to observe any potential association between brachial–ankle pulse wave velocity (BAPWV), a marker of arterial stiffness related to CVD risk, and Body Mass Index (BMI), a crude and widely used measure of obesity. Methods: Adult individuals (n = 857) assessed for routine CV risk were included and grouped according to their BMI (<25 kg/m²: normal; 25–30 kg/m²: overweight, ≥30 kg/m²: obese). Their anthropometric parameters, brachial cuff pressures, and BAPWV were measured. Results: Brachial pressure was significantly higher as BMI increased. BAPWV showed a positive linear association with systolic (r = 0.66, p < 0.01), mean (r = 0.60, p < 0.01), diastolic (r = 0.51, p < 0.01), and pulse (r = 0.53, p < 0.01) pressures. However, a linear relationship between BMI and BAPWV was only apparent in males aged <50 years (p = 0.01) and in females aged ≥50 years (p < 0.01). In individuals with similar brachial systolic pressure, BAPWV was higher in normal-weight subjects compared to overweight–obese ones. Conclusions: This conflicting finding is attributed to an overestimation of the degree of arterial stiffness as a measure of CVD risk in individuals with a less ‘healthy’ BMI. This suggests that BMI may not the appropriate obesity indicator to assess CV risk. Our finding emphasizes the importance of establishing a non-linear relationship between CVD risk, age, and BMI, taking into account apparent sex differences, to predict future CV events. While this finding may suggest a lower degree of stiffness in large arteries of overweight–obese subjects compared to their normal-weight counterparts, the potential implications for individuals with higher BMI need be explored further. Full article

In advanced heart failure (AHF) clinical evaluation fails to detect subclinical HF deterioration in outpatient settings. The aim of the study was to determine whether the strategy of intensive outpatient echocardiographic monitoring, followed by treatment modification, reduces mortality and re-hospitalizations at 12 months. Methods: 214 patients with ejection fraction < 30% and >1 hospitalization during the last year underwent clinical evaluation and echocardiography at discharge and were divided into intensive (IMG; N = 143) or standard monitoring group (SMG; N = 71). In IMG, volemic status and left ventricular filling pressure were assessed 14, 30, 90, 180 and 365 days after discharge. HF treatment, particularly diuretic therapy, was temporarily intensified when HF deterioration signs and E/e’ > 15 were detected. In SMG, standard outpatient monitoring without obligatory echocardiography at outpatient visits was performed. Results: We observed lower hospitalization (absolute risk reduction [ARR]-0.343, CI-95%: 0.287–0.434, p < 0.05; number needed to treat [NNT]-2.91) and mortality (ARR-0.159, CI 95%: 0.127–0.224, p < 0.05; NNT-6.29) in IMG at 12 months. One-year survival was 88.8% in IMG and 71.8% in SMG (p < 0.05). Conclusion: In AHF, outpatient monitoring of volemic status and intracardiac filling pressures to individualize treatment may potentially reduce hospitalizations and mortality at 12 months follow-up. Echocardiography-guided outpatient therapy is feasible and clinically beneficial, providing evidence for the larger application of this approach. Full article

Adult mammalian cardiomyocytes demonstrate scarce cycling and even lower proliferation rates in response to injury. Signals that enhance cardiomyocyte proliferation after injury will be groundbreaking, address unmet clinical needs, and represent new strategies to treat cardiovascular diseases. In vivo methods to monitor cardiomyocyte proliferation are critical to addressing this challenge. Fortunately, advances in transgenic approaches provide sophisticated techniques to quantify cardiomyocyte cycling and proliferation. Full article

Hypertension is the most frequent chronic and non-communicable disease all over the world, with about 1.5 billion affected individuals worldwide. Its impact is currently growing, particularly in low-income countries. Even in high-income countries, hypertension remains largely underdiagnosed and undertreated, with consequent low rates of blood pressure (BP) control. Notwithstanding the large number of clinical observational studies and randomized trials over the past four decades, it is sad to note that in the last few years there has been an impressive paucity of innovative studies. Research focused on BP mechanisms and novel antihypertensive drugs is slowing dramatically. The present review discusses some advances in the management of hypertensive patients, and could play a clinical role in the years to come. First, digital/health technology is expected to be increasingly used, although some crucial points remain (development of non-intrusive and clinically validated devices for ambulatory BP measurement, robust storing systems enabling rapid analysis of accrued data, physician-patient interactions, etc.). Second, several areas should be better outlined with regard to BP diagnosis and treatment targets. Third, from a therapeutic standpoint, existing antihypertensive drugs, which are generally effective and well tolerated, should be better used by exploiting available and novel free and fixed combinations. In particular, spironolactone and other mineral-corticoid receptor antagonists should be used more frequently to improve BP control. In particular, some drugs initially developed for conditions different from hypertension including heart failure and diabetes have demonstrated to lower BP significantly and should therefore be considered. Finally, renal artery denervation is another procedure that has proven effective in the management of hypertension. Full article

Therapeutic strategy utilizing mechanical circulatory supports in patients with pheochromocytoma-related cardiogenic shock remains unestablished. We had a 51-year-old man with acute decompensated heart failure due to pheochromocytoma crisis. He received a percutaneous left ventricular assist device-supported alpha-blocker and intensive fluid infusion therapy, which ameliorated impaired end-organ dysfunction, maintaining hemodynamics and achieving cardiac recovery, followed by the successfully scheduled adrenalectomy. Early suspicion of pheochromocytoma and Impella-supported disease-specific medical management might be a promising bridge to surgery strategy. Full article

Cardiovascular diseases (CVDs) are the major cause of death worldwide. Although the importance of conventional CVD risk factors, including older age, male gender, hypertension, obesity, dyslipidemia and hyperglycemia, is well-studied, psychosocial stress, which is considered an independent CVD risk factor, requires further investigation. Thus, we aimed to investigate the association between long-term secretion of stress-related steroid hormones, including cortisol, cortisone and dehydroepiandrosterone, and the 10-year fatal and non-fatal CVD risk estimated by the SCORE2 risk prediction algorithm, as well as traditional CVD risk factors in a group of apparently healthy women. A total of 145 women (aged 50–64 years) participating in the national CVD prevention program were enrolled in the study. Sociodemographic, lifestyle, health-related characteristics, stress, anxiety and sleep quality indicators were evaluated using specific questionnaires. Anthropometric and arterial blood pressure measures were assessed by trained personnel, lipid and glucose metabolism biomarkers were measured using routine methods, and hair steroid hormone levels were determined by ultra-high-performance liquid chromatography-tandem mass spectrometry. The results showed that higher levels of hair cortisol and cortisone are associated with increased SCORE2 values. Moreover, significant associations between hair glucocorticoids and individual cardiovascular risk factors, including obesity, hypertension, dyslipidemia and hyperglycemia, were found. These findings indicate that stress-related hair steroid hormones might be valuable biomarkers for CVD prediction and prevention. Full article

Background: Several works of observational clinical research indicate that coronary artery disease (CAD) and atrial fibrillation (AF) aggravate each other. However, it is unknown whether these associations reveal independent causal processes. Objective: The present study aimed to evaluate causal associations between CAD and AF using two-sample Mendelian randomization (TSMR) analysis. Methods: Summary-level Genome-wide association study (GWAS) data for CAD were obtained from the CARDIoGRAMplusC4D consortium, including 60,801 patients and 123,504 controls. General data for AF were acquired from the largest meta-analysis, comprising of 60,620 patients with AF and 970,216 non-cases. After data harmonization, three different methods—inverse-variance weighted (IVW), MR-Egger, and weighted-median—were applied for TSMR analysis. Results: The calculated ORs (95% CIs) for AF using IVW, MR-Egger, and weighted-median analysis were 1.11 (1.05, 1.17; p-value < 0.001), 1.14 (1.00, 1.29; p-value = 0.049), and 1.13 (1.08, 1.19; p-value < 0.001), respectively; for CAD, the results were 1.01 (0.97, 1.04; p-value = 0.76), 0.95 (0.89, 1.02; p-value = 0.15), and 1.00 (0.95, 1.05; p-value = 0.97). Conclusion: This comprehensive TSMR analysis provides evidence that patients with CAD are associated with an increased risk of AF. However, no causal association was found between patients with AF and the risk of CAD. These findings benefit clinical decision-making. Early heart-rhythm monitoring should be performed in patients with CAD. The prevention and treatment of AF complications such as thrombosis may be essential to reduce the incidence of CAD in AF patients. Full article

The left and right atria serve as buffer chambers to control the flow of venous blood for ventricular filling. If an atrium is absent, blood does not flow effectively into the ventricle, leading to venous blood retention and low cardiac output. The importance of atrial function has become increasingly recognized, because left atrial (LA) function contributes to cardiac performance, and loss of LA function is associated with heart failure. LA volume change has been used for LA function assessment in experimental and clinical studies. In conjunction with LA pressure, the LA pressure–volume relationship provides a better understanding of LA mechanics. LA strain measurement by speckle tracking echocardiography was introduced to evaluate three components of LA function as a (booster) pump, reservoir and conduit. Furthermore, increasing evidence supports the theory that LA reservoir strain has prognostic utility in various cardiac diseases. In this review, we summarize LA contribution to maintain cardiac performance by evaluating LA function with echocardiography according to our experiences and previous reports. Furthermore, we discuss LA dysfunction in challenging cardiac diseases of cardiac amyloidosis and adult congenital heart disease. Full article

The impact of sex on the assessment of congestion in acute heart failure (AHF) is still a matter of debate. The objective of this analysis was to evaluate sex differences in the evaluation of congestion at admission in patients hospitalized for AHF. We consecutively enrolled 494 AHF patients (252 female). Clinical congestion assessment, B-type natriuretic peptide levels analysis, blood urea nitrogen to creatinine ratio (BUN/Cr), plasma volume status estimate (by means of Duarte or Kaplam-Hakim PVS), and hydration status evaluation through bioimpedance analysis were performed. There was no difference in medications between men and women. Women were older (79 ± 9 yrs vs. 77 ± 10 yrs, p = 0.005), and had higher left ventricular ejection fraction (45 ± 11% vs. 38 ± 11%, p < 0.001), and lower creatinine clearance (42 ± 25 mL/min vs. 47 ± 26 mL/min, p = 0.04). The prevalence of peripheral oedema, orthopnoea, and jugular venous distention were not significantly different between women and men. BUN/Cr (27 ± 9 vs. 23 ± 13, p = 0.04) and plasma volume were higher in women than men (Duarte PVS: 6.0 ± 1.5 dL/g vs. 5.1 ± 1.5 dL/g, p < 0.001; Kaplam–Hakim PVS: 7.9 ± 13% vs. −7.3 ± 12%, p < 0.001). At multivariate logistic regression analysis, female sex was independently associated with BUN/Cr and PVS. Female sex was independently associated with subclinical biomarkers of congestion such as BUN/Cr and PVS in patients with AHF. A sex-guided approach to the correct evaluation of patients with AHF might become the cornerstone for the correct management of these patients. Full article

Throughout the last decades, newly developed chemotherapeutic agents and immunotherapies that target signaling pathways have provided patients with better prognoses, improved their quality of life and increased survival rates, thus converting cancer to a stable chronic disease. However, non-anthracycline cancer chemotherapy agents and immunotherapies including human epidermal growth factor receptor 2 (HER2) inhibitors, vascular endothelial growth factor (VEGF) inhibitors, Bcr-Abl tyrosine-kinase inhibitors (TKI), proteasome inhibitors, immune checkpoint inhibitors and chimeric antigen receptor T cells (CAR-T cells) may cause cardiovascular toxicity events and complications that usually interrupt the continuation of an appropriate treatment regimen, which induces life-threatening risks or leads to long-term morbidity. Heart failure, cardiac arrythmias and cardiomyopathies are the most common cardiovascular events related to cardiotoxicity due to chemotherapy. Each patient should be carefully assessed and monitored before, during and after the administration of chemotherapy, to address any predisposing risk factors and the new onset of cardiotoxicity manifestations early and treat them appropriately. The development of novel anticancer agents that cause minimal cardiovascular toxicity events or novel agents that ameliorate the adverse effects of the existing anticancer agents could drastically change the field of cardio-oncology. The aim of this narrative review is to demonstrate new knowledge regarding the screening and diagnosis of non-anthracycline-induced cardiotoxicity and to propose protective measures that could be performed in order to achieve the delivery of optimal care. Full article

Neonatal dilated cardiomyopathy (DCM) is rare with high etiologic heterogeneity. Recently, biallelic, autosomal recessive, pathogenic variants in RPL3L (ribosomal protein L3-like) have been reported in the literature with severe early-onset DCM. In the present brief report, we identified two pathogenic RPL3L variants, each harbored in unaffected heterozygous parents: mother (RPL3L c.1076_1080delCCGTG (p.Ala359Glyfs*4)) and father (RPL3L c.80G > A (p.Gly27Asp)). Pathogenic variants were segregated as autosomal recessive to two offspring born with compound heterozygous RPL3L variants and affected by neonatal DCM. This is the second report in the literature to the best of our knowledge and our findings support the pathogenicity of biallelic RPL3L pathologic variants associated with rapidly progressive neonatal DCM and heart failure with a poor prognosis. Full article