Cardiovascular Disease in 2023: Coronary Syndrome, Heart Failure and Structural Heart Disease

The endothelium is a continuous layer of cells that coats the interior walls of arteries, capillaries, and veins. It has an essential regulatory role in hemostatic function, vascular tone, inflammation, and platelet activity. Endothelial dysfunction is characterized by a shift to a proinflammatory and prothrombic state, and it could have a bidirectional relationship with heart failure (HF). Due to neurohormonal activation and shear stress, HFrEF may promote endothelial dysfunction, increase ROS synthesis, and reduce nitric oxide production. Different studies have also shown that endothelium function is damaged in HFpEF because of a systemic inflammatory state. Some clinical trials suggest that drugs that have an effect on endothelial dysfunction in patients with HF or cardiovascular disease may be a therapeutic option. The aim of this review is to highlight the pathogenetic correlation between endothelial dysfunction and heart failure and the related potential therapeutic options. Full article

Background and aim: There are few prospective data on the prognostic value of normal admission low-density lipoprotein cholesterol (LDL-C) in statin-naïve patients with acute coronary syndromes (ACS) who are treated with a preemptive invasive strategy. We aimed to analyze the proportion of patients with normal LDL-C at admission for ACS in our practice, and their characteristics and clinical outcomes in comparison to patients with high admission LDL-C. Patients and methods: Two institutions’ prospective registries of patients with confirmed ACS from Jan 2017 to Jan 2023 were used to identify 1579 statin-naïve patients with no history of prior coronary artery disease (CAD), and with available LDL-C admission results, relevant clinical and procedural data, and short- and long-term follow-up data. Normal LDL-C at admission was defined as lower than 2.6 mmol/L. All demographic, clinical, procedural, and follow-up data were compared between patients with normal LDL-C and patients with a high LDL-C level (≥2.6 mmol/L) at admission. Results: There were 242 (15%) patients with normal LDL-C at admission. In comparison to patients with high LDL-cholesterol at admission, they were significantly older (median 67 vs. 62 years) with worse renal function, had significantly more cases of diabetes mellitus (DM) (26% vs. 17%), peripheral artery disease (PAD) (14% vs. 9%), chronic obstructive pulmonary disease (COPD) (8% vs. 2%), and psychological disorders requiring medical attention (19% vs. 10%). There were no significant differences in clinical type of ACS. Complexity of CAD estimated by coronary angiography was similar between the two groups (median Syntax score 12 for both groups). There were no significant differences in rates of complete revascularization (67% vs. 72%). Patients with normal LDL-C had significantly lower left ventricular ejection fraction (LVEF) at discharge (median LVEF 52% vs. 55%). Patients with normal LDL-C at admission had both significantly higher in-hospital mortality (5% vs. 2%, RR 2.07, 95% CI 1.08–3.96) and overall mortality during a median follow-up of 43 months (27% vs. 14%, RR 1.86, 95% CI 1.45–2.37). After adjusting for age, renal function, presence of diabetes mellitus, PAD, COPD, psychological disorders, BMI, and LVEF at discharge in a multivariate Cox regression analysis, normal LDL-C at admission remained significantly and independently associated with higher long-term mortality during follow-up (RR 1.48, 95% CI 1.05–2.09). Conclusions: A spontaneously normal LDL-C level at admission for ACS in statin-naïve patients was not rare and it was an independent risk factor for both substantially higher in-hospital mortality and mortality during long-term follow-up. Patients with normal LDL-C and otherwise high total cardiovascular risk scores should be detected early and treated with optimal medical therapy. However, additional research is needed to reveal all the missing pieces in their survival puzzle after ACS—beyond coronary anatomy, PCI optimization, numerical LDL-C levels, and statin therapy. Full article

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24–48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients. Full article

Background and Objectives: Patients presenting with ST Elevation Myocardial Infarction (STEMI) due to occlusive coronary arteries remain at a higher risk of excess morbidity and mortality despite being treated with primary percutaneous coronary intervention (PPCI). Identifying high-risk patients is prudent so that close monitoring and timely interventions can improve outcomes. Materials and Methods: A cohort of 605 STEMI patients [64.2 ± 13.2 years, 432 (71.41%) males] treated with PPCI were recruited. Their arterial pressure (AP) wave recorded throughout the PPCI procedure was analyzed to extract features to predict 1-year mortality. After denoising and extracting features, we developed two distinct feature selection strategies. The first strategy uses linear discriminant analysis (LDA), and the second employs principal component analysis (PCA), with each method selecting the top five features. Then, three machine learning algorithms were employed: LDA, K-nearest neighbor (KNN), and support vector machine (SVM). Results: The performance of these algorithms, measured by the area under the curve (AUC), ranged from 0.73 to 0.77, with accuracy, specificity, and sensitivity ranging between 68% and 73%. Moreover, we extended the analysis by incorporating demographics, risk factors, and catheterization information. This significantly improved the overall accuracy and specificity to more than 76% while maintaining the same level of sensitivity. This resulted in an AUC greater than 0.80 for most models. Conclusions: Machine learning algorithms analyzing hemodynamic traces in STEMI patients identify high-risk patients at risk of mortality. Full article

Background: Although ranolazine has been available for years as a second-line treatment to reduce angina attacks in patients with stable angina pectoris, real-world data on the effectiveness, tolerability, and safety of ranolazine are limited. Methods: A non-interventional, prospective study was conducted to assess the effectiveness and safety of ranolazine. Patients eligible for enrolment had a baseline assessment between one and fourteen days after initiating ranolazine for the first time and a follow-up visit three months later. The primary endpoints comprised the weekly frequency of angina attacks, total adverse events, and ranolazine discontinuation rate. The secondary endpoints included the use of short-acting nitrates, changes on the Canadian Cardiovascular Society (CCS) angina classification score and quality of life scale score (QoL). Results: In total, 1101 patients were enrolled at 214 sites. Mean weekly angina attacks were reduced from 3.6 ± 2.9 to 0.4 ± 0.9 (p < 0.0001) and the mean weekly consumption of short-acting nitrates decreased by 1.7 ± 2.2 (p < 0.0001). CCS class and QoL were also improved (p < 0.0001). Adverse events were reported by 11 (1%) patients in total, while 2 of them (0.2%) were characterised as serious. Treatment was discontinued for various reasons in 23 patients (2.1%) after the follow-up period. Ranolazine treatment was equally effective in all subgroups tested, with larger benefits observed in patients with more frequent angina and CCS angina class III and IV. Up-titration of ranolazine during the study improved the outcomes. Conclusions: Ranolazine was well tolerated and effectively reduced angina attacks, with simultaneous improvement of the CCS class and QoL score in patients with stable angina. Full article

Most anesthetics reduce cardiac functions and lower blood pressure (BP), potentially causing excessive BP reduction in dehydrated patients or those with heart conditions, such as coronary artery disease (CAD). Considering the increased prevalence of cardiovascular disease with age, anesthesiologists must be cautious about BP reduction during general anesthesia in older adults. In the present case, a 76-year-old male patient with undiagnosed CAD in a hypovolemic state experienced a significant drop in systolic BP to the fifties during propofol and sevoflurane anesthesia. Despite the use of vasopressors, excessive hypotension persisted, leading to anesthesia suspension. Subsequent cardiac examinations, including computed tomography heart angio and calcium score, and coronary angiogram, revealed a near total occlusion of the proximal left anterior descending coronary artery (pLAD) and the formation of collateral circulation. After 5 days of hydration and anticoagulation medications and confirmation of normovolemic state, general anesthesia was attempted again and successfully induced; a normal BP was maintained throughout the surgery. Thus, it is important to conduct a thorough cardiac evaluation and maintain normovolemia for general anesthesia in older adults. Full article

Non-valvular atrial fibrillation (NVAF) is the most common cardiac arrhythmia in the general population, and its prevalence increases among patients with chronic kidney disease (CKD) undergoing hemodialysis. This population presents high risk of both hemorrhagic and thrombotic events, with little evidence regarding the use of oral anticoagulation treatment (OAT) and multiple complications arising from it; however, stroke prevention with percutaneous left atrial appendage closure (LAAC) is an alternative to be considered. We retrospectively describe the safety and efficacy of percutaneous LAAC in eight patients with NVAF and CKD on hemodialysis during a 12-month follow-up. The mean age was 78.8 years (range 64–86; SD ± 6.7), and seven patients were male. The mean CHA₂DS₂-VAS_C and HAS-BLED scores were high, 4.8 (SD ± 1.5) and 3.8 (SD ± 1.3), respectively. Seventy-five percent of the patients were referred for this intervention due to a history of major bleeding, with gastrointestinal bleeding being the most common type, while the remaining twenty-five percent of the patients were referred because of a high risk of bleeding. The percutaneous LAAC procedure was successfully completed in 100% of the patients, with complete exclusion of the appendage without complications or leaks exceeding 5 mm. There was one death not related to the procedure four days after the intervention. Among the other seven patients, no deaths, cardioembolic events or major bleeding were reported during the follow-up period. In our sample, percutaneous LAAC appears to be a safe and effective alternative to anticoagulation in patients with NVAF and CKD on hemodialysis. Full article

Background: People living with human immunodeficiency virus (HIV) (PLWH) have increased risk of developing diastolic dysfunction (DD) and heart failure with preserved ejection fraction (EF). In this observational study, we evaluated DD and left ventricular hypertrophy (LVH) in PLWH receiving antiretroviral therapy (ART) with undetectable viremia. Methods: We conducted an observational study. All participants underwent transthoracic echocardiography to assess chamber size and systolic and diastolic function. Results: Most patients showed concentric remodeling without LVH. All patients had normal left ventricle systolic function (EF median 61.3%, interquartile range: 57.8–66.2). None fulfilled the DD criteria, while two patients (6%) had undetermined diastolic function. Twenty percent (n = 7) of patients had an enlarged left atrium (left atrium volume index [LAVI] > 34 cm³/m²). These patients had a significantly lower CD4⁺ count (771.53 ± 252.81 vs. 446.00 ± 219.02, p = 0.01) and higher relative wall thickness (0.50 ± 0.05 vs. 0.44 ± 0.06, p = 0.03). Patients without immune restoration above 500 cells/μL had significantly higher LAVI (33.92 ± 6.63 vs. 24.91 ± 7.03, p = 0.01). Conclusions: One-fifth of patients had left atrial enlargement associated with worse immune restoration during ART treatment. The mechanism of left atrial enlargement and its association with cardiovascular risk require further investigations. Full article

Aspirin has for some time been used as a first-line treatment for acute coronary syndromes, including ST-elevation myocardial infarction, for secondary prevention of established coronary disease, and for primary prevention in patients at risk of coronary artery disease. Although aspirin has been in use for decades, the available evidence for its efficacy largely predates the introduction of other drugs, such as statins and P2Y12 inhibitors. Based on recent trials, the recommendation for aspirin use as primary prevention has been downgraded. In addition, P2Y12 inhibitors given as a single antiplatelet therapy have been associated with a lower incidence of bleeding than dual antiplatelet therapy in combination with aspirin in patients with stable and unstable coronary artery disease. The aim of this review is to discuss the role of aspirin considering the available evidence for primary prevention, secondary prevention for stable coronary artery disease or acute coronary syndromes, and after percutaneous coronary intervention or coronary artery bypass revascularization. Full article

Trastuzumab is the primary treatment for all stages of HER2-overexpressing breast cancer in patients. Though discovered over 20 years ago, trastuzumab-induced cardiotoxicity (TIC) remains a research topic in cardio-oncology. This review explores the pathophysiological basis of TIC and its clinical manifestations. Their understanding is paramount for early detection and cardioprotective treatment. Trastuzumab renders cardiomyocytes susceptible by inhibiting the cardioprotective NRG-1/HER2/HER4 signaling pathway. The drug acts on HER2-receptor-expressing cardiomyocytes, endothelium, and cardiac progenitor cells (see the Graphical Abstract). The activation of immune cells, fibroblasts, inflammation, and neurohormonal systems all contribute to the evolution of TIC. A substantial amount of research demonstrates that trastuzumab induces overt and subclinical left ventricular (LV) systolic failure. Data suggest the development of right ventricular damage, LV diastolic dysfunction, and heart failure with preserved ejection fraction. Further research is needed to define a chronological sequence of cardiac impairments to guide the proper timing of cardioprotection implementation. Full article

We sought to investigate the impact of heart failure on anti-spike antibody positivity following SARS-CoV-2 vaccination. Our study included 103 heart failure (HF) patients, including those with and without left ventricular assist devices (LVAD) selected from our institutional transplant waiting list as well as 104 non-heart failure (NHF) patients who underwent open heart surgery at our institution from 2021 to 2022. All the patients received either heterologous or homologous doses of BNT162b2 and CoronaVac. The median age of the HF group was 56.0 (interquartile range (IQR): 48.0–62.5) and the NHF group was 63.0 (IQR: 56.0–70.2) years, and the majority were males in both groups (n = 78; 75.7% and n = 80; 76.9%, respectively). The majority of the patients in both the HF and NHF groups received heterologous vaccinations (n = 43; 41.7% and n = 52; 50.3%, respectively; p = 0.002). There was no difference in the anti-spike antibody positivity between the patients with and without heart failure (p = 0.725). Vaccination with BNT162b2 led to significantly higher antibody levels compared to CoronaVac alone (OR: 11.0; 95% CI: 3.8–31.5). With each passing day after the last vaccine dose, there was a significant decrease in anti-spike antibody positivity, with an OR of 0.9 (95% CI: 0.9–0.9). Furthermore, hyperlipidemia was associated with increased antibody positivity (p = 0.004). Full article

Background and Objectives: Patients with chronic total occlusions of the coronary arteries are either treated with PCI or referred for surgical revascularization. We analyzed the patients with chronic occluded coronary arteries that were surgically treated and aimed to describe the anatomical characteristics, revascularization rates, and in-hospital outcomes achieved with coronary artery bypass grafting. Methods: Angiographic data of 2005 patients with coronary artery disease treated in our institution between January 2005 and December 2014 were retrospectively analyzed. A total of 1111 patients with at least one coronary total occlusion were identified. We reviewed the preoperative coronary angiograms and surgical protocols to determine the presence, localization, and revascularization of coronary occlusions. We also evaluated the perioperative data and in-hospital outcomes. Results: The median age of the study population was 68 years (25th–75th percentiles, 61.0–74.0). Three-vessel disease was present in 94.8% of patients and the rest (5.8%) had a two-vessel disease. The localizations of the occlusions were as follows: 68.4% in the RCA system, 26.4% in the LAD, and 28.5% in the LCX system. Multiple occlusions were present in 22.6% of the patients. Complete coronary total occlusion revascularization was achieved in 86.1% of the patients. The overall in-hospital mortality was 2.3%. The median in-hospital stay was 14.0 days. After logistic regression analysis, age (odds ratio 3.44 [95% confidence interval, 1.81–6.53], p < 0.001, for a 10-year increase) and the presence of peripheral artery disease (odds ratio 3.32 [1.39–7.93], p = 0.007) were the only statistically significant independent predictors of in-hospital mortality. Conclusions: A high revascularization rate and favorable in-hospital outcomes are achieved with coronary artery bypass surgery in patients with multi-vessel diseases and coronary total occlusions. Older age and the presence of peripheral artery disease are independent predictors of in-hospital mortality. A long-term follow-up and the type of graft (arterial vs. venous) used would bring more useful data for this type of revascularization. Full article

Purpose: Recent years have seen a clear link established between elevated ferritin levels and COVID-19 prognosis. However, the impact of heightened ferritin levels on the prognosis of individuals with severe ischemic heart disease remains uncertain. Methods: We utilized the MIMIC IV database to identify a cohort of ischemic heart disease patients who underwent serum ferritin testing. We conducted regression analyses, employed the overlap propensity score weighting model, and utilized the restricted cubic splines model to comprehensively investigate the associations between serum ferritin levels and clinical outcomes. Results: Our cohort included 1173 patients with diagnosed ischemic heart disease, categorized into high and low serum ferritin groups. After meticulous adjustment for confounding factors in a fully adjusted model, the hazard ratios (HRs) for 90-day and 1-year mortality were 1.63 (95% CI: 1.27–2.09) and 1.49 (95% CI: 1.19–1.86), respectively, in the high-ferritin group compared to the low-ferritin group. Subsequent analyses with propensity score weighting confirmed these results. Remarkably, restricted cubic spline analysis revealed an almost linear relationship between log-transformed serum ferritin levels and the risk of both 90-day and 1-year all-cause mortality. Moreover, incorporating ferritin into conventional severity of illness scores significantly improved the area under the curve for both 90-day and 1-year mortality. Conclusions: This study provides compelling evidence regarding the prognostic significance of serum ferritin in predicting 90-day and one-year mortality rates among patients diagnosed with ischemic heart disease. Full article

Heart failure (HF) is a progressive condition with an increasing prevalence, and the scientific evidence of heart failure with reduced ejection fraction (HFrEF) reports a 6% rate of 1-year mortality in stable patients, whereas, in recently hospitalized patients, the 1-year mortality rates exceed 20%. The Sacubitril/Valsartan (S/V), the first angiotensin receptor neprilysin inhibitor (ARNI), significantly reduced both HF hospitalization and cardiovascular mortality. Aim of the study: to evaluate the effect of S/V in a follow-up period of 5 years from the beginning of the therapy. We compared the one-year outcomes of S/V use with those obtained after 5 years of therapy, monitoring the long-term effects in a real-world population with HFrEF. Methods: Seventy consecutive patients with HFrEF and eligible for ARNI, according to PARADIGM-HF criteria, were enrolled. All patients had an overall follow-up of 60 months, during which time they underwent standard transthoracic echocardiography (TTE) with Global Longitudinal Strain (GLS) evaluation, the Kansas City Cardiomyopathy Questionnaire (KCCQ), the Six Minutes Walking Test (6MWT), and blood tests (NT-pro-BNP and BNP, renal function tests). Results: NTproBNP values were reduced significantly among the three time-points (p < 0.001). Among echocardiographic parameters, left ventricle end-diastolic volume (LV EDV) and E/e’ significantly were reduced at the first evaluation (12 months), while left ventricle end-systolic volume (LV ESV) decreased during all follow-ups (p < 0.001). LV EF (p < 0.001) and GLS (p < 0.001) significantly increased at both evaluations. The 6MWT (p < 0.001) and KCCQ scores (p < 0.001) increased significantly in the first 12 months and remained stable along the other time-points. NYHA class showed an increase in class 1 subjects and a decrease in class 3 subjects during follow-up. NTproBNP, BNP, 6MWT, and KCCQ scores showed a significant change in the first 12 months, while LVEF, GLS, and ESV changed during all evaluations. Conclusions: We verified that the improvements obtained after one year of therapy had not reached a plateau phase but continued to improve and were statistically significant at 5 years. Although our data should be confirmed in larger and multicentre studies, we can state that the utilization of Sacubitril/Valsartan has catalysed substantial transformations in the prognostic landscape of chronic HFrEF, yielding profound clinical implications. Full article

Introduction: The aim of this study was to assess clinical outcomes and quality of life after PFO closure in patients with previous stroke/TIA of undetermined cause and in patients with other complex PFO-associated clinical conditions. Methods: Between July 2009 and December 2019 at our University Cardiology Department, 118 consecutive patients underwent a thorough diagnostic work-up including standardized history taking, clinical evaluation, full neurological examination, screening for thrombophilia, brain magnetic resonance imaging (MRI), ultrasound–Doppler sonography of supra-aortic vessels and 24 h ECG Holter monitoring. Anatomo-morphological evaluation using 2D transthoracic/transesophageal echocardiography (TTE/TEE) color Doppler and functional assessment using contrast TTE (cTTE) in the apical four-chamber view and contrast transcranial Doppler (cTCD) using power M-mode modality were performed to verify the presence, location and amount of right-to-left shunting via PFO or other extracardiac source. Completed questionnaires based on the Quality-of-Life Short Form-36 (QoL SF-36) and Migraine Disability Assessment (MIDAS) were obtained from the patients before PFO closure and after 12 months. Contrast TTE/TEE and cTCD were performed at dismission, 1, 6 and 12 months and yearly thereafter. Brain MRI was performed at 1-year follow-up in 54 patients. Results: Transcatheter PFO closure was performed in 106 selected symptomatic patients (mean age 41.7 ± 10.7 years, range 16–63, 65% women) with the following conditions: ischemic stroke (n = 23), transient ischemic attack (n = 22), peripheral and coronary embolism (n = 2), MRI lesions without cerebrovascular clinical events (n = 53), platypnea–orthodeoxia (n = 1), decompression sickness (n = 1) and refractory migraine without ischemic cerebral lesions (n = 4). The implanted devices were Occlutech Figulla Flex I/II PFO (n = 99), Occlutech UNI (n = 3), Amplatzer PFO (n = 3) and CeraFlex PFO occluders (n = 1). Procedures were performed under local anesthesia and rotational intracardiac monitoring (Ultra ICE) alone. The devices were correctly implanted in all patients. The mean fluoroscopy time was 15 ± 5 min (range = 10–45 min) and the mean procedural time was 55 ± 20 min (range = 35–90 min). The total occlusion rate at follow-up (mean 50 months, range 3–100) was 98.1%. No recurrent neurological events were observed in the long-term follow-up. Conclusions: The data collected in this study demonstrate that percutaneous PFO closure is a safe and effective procedure, showing long-term prevention of recurrent cerebrovascular events, significant reduction in migraine symptoms and substantial improvement in quality of life. Full article

Background and Objectives: Sutureless aortic valve prostheses have presented favorable hemodynamic performance while facilitating minimally invasive access approaches. As the population ages, the number of patients at risk for aortic valve reoperation constantly increases. The aim of the present study is to present our single-center experience in sutureless aortic valve replacement (SU-AVR) in reoperations. Materials and Methods: The data of 18 consecutive patients who underwent SU-AVR in a reoperation between May 2020 and January 2023 were retrospectively analyzed. Results: The mean age of the patients was 67.9 ± 11.1 years; patients showed a moderate-risk profile with a median logistic EuroSCORE II of 7.8 (IQR of 3.8–32.0) %. The implantation of the Perceval S prosthesis was technically successful in all patients. The mean cardiopulmonary bypass time was 103.3 ± 50.0 min, and the cross-clamp time was 69.1 ± 38.8 min. No patients required a permanent pacemaker implantation. The postoperative gradient was 7.3 ± 2.4 mmHg, and no cases of paravalvular leakage were observed. There was one case of intraprocedural death, while the thirty-day mortality was 11%. Conclusions: Sutureless bioprosthetic valves tend to simplify the surgical procedure of a redo AVR. By maximizing the effective orifice area, sutureless valves may present an important advantage, being a safe and effective alternative not only to traditional surgical prostheses but also to transcatheter valve-in-valve approaches in select cases. Full article

Background: Transcatheter aortic valve implantation (TAVI) has developed as an alternative to surgery for symptomatic high-risk patients with aortic stenosis (AS). An important complication of TAVI is acute kidney injury. The purpose of the study was to investigate if the Mehran Score (MS) could be used to predict acute kidney injury (AKI) in TAVI patients. Methods: This is a multicenter, retrospective, observational study including 1180 patients with severe AS. The MS comprised eight clinical and procedural variables: hypotension, congestive heart failure class, glomerular filtration rate, diabetes, age >75 years, anemia, need for intra-aortic balloon pump, and contrast agent volume use. We assessed the sensitivity and specificity of the MS in predicting AKI following TAVI, as well as the predictive value of MS with each AKI-related characteristic. Results: Patients were categorized into four risk groups based on MS: low (≤5), moderate (6–10), high (11–15), and very high (≥16). Post-procedural AKI was observed in 139 patients (11.8%). MS classes had a higher risk of AKI in the multivariate analysis (HR 1.38, 95% CI, 1.43–1.63, p < 0.01). The best cutoff for MS to predict the onset of AKI was 13.0 (AUC, 0.62; 95% CI, 0.57–0.67), whereas the best cutoff for eGFR was 42.0 mL/min/1.73 m² (AUC, 0.61; 95% CI, 0.56–0.67). Conclusions: MS was shown to be a predictor of AKI development in TAVI patients. Full article

Transcatheter aortic valve implantation (TAVI) is currently becoming the method of choice in high-risk patients with severe aortic valve stenosis. Post-TAVI complications are more common owing to the increasing use of the method. The majority of TAVI complications derive from concomitant aortic stenosis with moderate/severe aortic insufficiency, paravalvular leak, and atrioventricular block. The contemporary TAVI qualification process includes a thorough echocardiography and angio-CT of the aorta, which is crucial in assessing valve measurements, determining the position of the coronary arteries branching from the aorta, and choosing the optimal valve size. We present the case report of an 81-year-old patient admitted to our hospital because of exacerbation of the clinical condition and development of pulmonary edema a few days after TAVI. Despite the reduction of the initial leak, an echocardiographic examination revealed the remaining severe paravalvular aortic leakage. We performed open-heart cardio-thoracic surgery, explanted the TAVI valve, and implanted the biological prosthesis (Edwards Perimount Magna size 25). Introduction of new interventional treatment approaches and the availability of imaging tools have substantially reduced the incidence of significant paravalvular leak and offered a better prognosis for patients undergoing TAVI. Full article

The precise association of serum leptin (Lep) with the body mass index (BMI) and blood pressure (BP) is not well known for understanding their involvement in health and disease. Hence, the present study was conducted to investigate the association of BP, BMI and serum Lep levels in young normal-weight (NW) and overweight (OW) male Saudi students. The NW (n: 198) and OW (n: 192) male subjects in the age range of 18–20 years were consulted. The BP was measured with a mercury sphygmomanometer. Leptin Human ELISA Kits were employed for the determination of the serum Lep levels. The mean ± SD values of BMI (kg/m²), Lep (ng/mL), systolic BP (SBP; mmHg), and diastolic BP (DBP; mmHg) all showed significant differences for young OW vs. NW subjects as: 27.52 ± 1.42 vs. 21.49 ± 2.03; 10.70 ± 4.67 vs. 4.68 ± 1.91; 121.37 ± 2.59 vs. 118.51 ± 1.54 and 81.44 ± 1.97 vs. 78.79 ± 1.44, respectively. All associations (among BMI, Lep, SBP and DBP) showed a positive linear and significant correlation, except the nonsignificant correlation of BMI and SBP for the NW group. Other variables showing significant variation for NW vs. OW subjects were: interleukin-6, high sensitivity C-reactive protein, apelin (APLN) and resistin. Serum APLN correlated significantly with Lep, BMI, SBP and DBP in lower and higher levels of BMI, with considerable progressive patterns in both the NW and OW groups and subgroups. The present study in young Saudi male students presents significant variations for BP and serum leptin levels, and a significant positive linear association among serum leptin, BMI and BP. Full article

Background and Objectives: The role of coronary artery bypass grafting (CABG) on postoperative left ventricular (LV) function in patients with preoperatively preserved left ventricular ejection fraction (LVEF) is still being discussed and only a few studies address this question. This study aimed to assess LV function after CABG in patients with preoperatively preserved LVEF using left ventricular longitudinal strain assessed by 2D speckle tracking imaging (STI). Materials and Methods: Fifty-nine consecutive adult patients with coronary artery disease (CAD) referred for a first-time elective CABG surgery were enrolled in the final analysis of this prospective single-center clinical study. Transthoracic echocardiography (TTE), with conventional measures and STI measures, was performed within 1 week before CABG as well as 4 months after surgery. Patients were divided into groups based on their preoperative global longitudinal strain (GLS) value. Differences in systolic and diastolic parameters between groups were analyzed. Results: Preoperative GLS was reduced (GLS < −17%) in 39% of the patients. Parameters of systolic LV function were significantly reduced in this group of patients compared to the patient group with GLS% ≥ −17%. In both groups, 4 months after CABG there was a decline in LVEF but statistically significant only in the group with GLS% ≥ −17% (p = 0.035). In patients with reduced GLS, there was a statistically significant postoperative improvement (p = 0.004). In patients with preoperative normal GLS, there was not a significant change in any strain parameters after CABG. There was an improvement in diastolic function parameters measured by Tissue Doppler Imaging (TDI) in both groups. Conclusions: There is improvement in LV systolic and diastolic function after CABG in patients with preserved preoperative LVEF measured by STI and TDI. GLS might be more sensitive and effective than LVEF for monitoring improvements in myocardial function after CABG surgery in patients with preserved LVEF. Full article

Type 2 diabetes (T2D) confers a high risk of heart failure frequently with evidence of cardiovascular structural and functional abnormalities before symptom onset. The effects of remission of T2D on cardiovascular structure and function are unknown. The impact of the remission of T2D, beyond weight loss and glycaemia, on cardiovascular structure and function and exercise capacity is described. Adults with T2D without cardiovascular disease underwent multimodality cardiovascular imaging, cardiopulmonary exercise testing and cardiometabolic profiling. T2D remission cases (Glycated hemoglobin (HbA1c) < 6.5% without glucose-lowering therapy, ≥3 months) were propensity score matched 1:4 based on age, sex, ethnicity and time of exposure to those with active T2D (n = 100) with the nearest-neighbour method and 1:1 with non-T2D controls (n = 25). T2D remission was associated with a lower leptin–adiponectin ratio, hepatic steatosis and triglycerides, a trend towards greater exercise capacity and significantly lower minute ventilation/carbon dioxide production (VE/VCO2 slope) vs. active T2D (27.74 ± 3.95 vs. 30.52 ± 5.46, p < 0.0025). Evidence of concentric remodeling remained in T2D remission vs. controls (left ventricular mass/volume ratio 0.88 ± 0.10 vs. 0.80 ± 0.10, p < 0.025). T2D remission is associated with an improved metabolic risk profile and ventilatory response to exercise without concomitant improvements in cardiovascular structure or function. There is a requirement for continued attention to risk factor control for this important patient population. Full article

Background and Objectives: Available data with regard to the outcomes of patients with severely calcified left main (LM) lesions after revascularization by percutaneous coronary intervention (PCI) when compared to non-calcified LM lesions is unclear. Materials and Methods: The present study sought to retrospectively investigate in hospital and 1 year post-intervention outcomes of patients with extremely calcified LM lesions after PCI facilitated by calcium-dedicated devices (CdD). Seventy consecutive patients with LM PCI were included. CdD requirement was based on suboptimal results after balloon angioplasty. Results: Twenty-two patients (31.4%) required at least one CdD, while nine patients (12.8%) required at least two. Intravascular lithotripsy and rotational atherectomy were the predominantly used methods(59.1% and 40.9% respectively, for in-group ratios), while ultra-high pressure and scoring balloons contributed the least to lesion preparation (9%). In 20 patients (28.5%), severe or moderate calcifications were angiographically identified, but non-compliant balloon predilation was adequate and CdD were not necessary. Total procedural time was significantly higher in CdD group (p-value 0.02). Procedural and clinical success were obtained in 100% of cases. There were no major adverse cardiac and cerebrovascular events (MACCE) recorded during hospitalization. MACCE at 1 year post-procedure were recorded in three patients (4.2% overall). All three events were documented in the control group (6.2%), and no events were recorded in CdD group (p-value 0.23). There was one cardiac death at 10 months and two target lesion revascularizations for side-branch restenosis. Conclusions: Patients with extremely calcified LM lesions treated by PCI present a favorable prognosis if angioplasty is facilitated by more aggressive lesion debulking using calcium-dedicated devices. Full article

Kawasaki disease (KD) is an acute vasculitis with an intrinsic risk of severe involvement of coronary arteries. The worldwide spread of KD and the importance of early diagnosis for preventing cardiovascular complications have ascertained the need for updating guidelines for prompt disease recognition and treatment efficacy assessment. All KD patients who comply with the definition of classic or atypical disease should be treated with intravenous immunoglobulin (IVIG) soon after diagnosis. The objective of our narrative review was to analyze the medical literature about case reports with atypical KD in relation to diagnosis and potential identification of predictors of non-responsiveness to IVIG. Our analysis has shown that the seminal challenge in KD management is the timeliness of diagnosis, although both extreme variability and transience of clinical manifestations make this goal difficult. A non-negligible percentage of patients, especially in the first 6 months of life, might have atypical manifestations of KD, whose painstaking differential diagnosis may be tricky. Many attempts to develop universal scoring systems and detect children at higher risk of IVIG resistance have been rather unsuccessful. Additionally, KD may show different evolutions according to unraveled demographic, genetic, or epigenetic factors. Further research is needed to elucidate all open questions about KD and clarify the long-term outcome of its potential complications. Full article

Background: Cardiomyopathies (CMs) are a heterogeneous and severe group of diseases that shows a highly variable cardiac phenotype and an incidence of app. 1/100.000. Genetic screening of family members is not yet performed routinely. Patients and methods: Three families with dilated cardiomyopathy (DCM) and pathogenic variants in the troponin T2, Cardiac Type (TNNT2) gene were included. Pedigrees and clinical data of the patients were collected. The reported variants in the TNNT2 gene showed a high penetrance and a poor outcome, with 8 of 16 patients dying or receiving heart transplantation. The age of onset varied from the neonatal period to the age of 52. Acute heart failure and severe decompensation developed within a short period in some patients. Conclusion: Family screening of patients with DCM improves risk assessment, especially for individuals who are currently asymptomatic. Screening contributes to improved treatment by enabling practitioners to set appropriate control intervals and quickly begin interventional measures, such as heart failure medication or, in selected cases, pulmonary artery banding. Full article

(1) Background: Receiving the first internal electric shock is a turning point for patients with an implantable cardioverter defibrillator (ICD) for primary prevention. However, no study has investigated whether patients who receive a first device-delivered electric shock have a poor prognosis even at the time of ICD implantation. (2) Methods: We retrospectively identified 55 patients with ischemic (n = 31) or dilated (n = 24) cardiomyopathy who underwent ICD implantation for primary prevention with exercise test at the time of implantation. We recorded baseline characteristics, exercise test parameters, and clinical events. (3) Results: After a median follow-up of 5 years, we observed an association between an appropriate device-delivered electric shock, the occurrence of death or heart transplant, and the occurrence of the composite endpoint. There was also a significant relation between a VE/VCO₂ slope >35 and the occurrence of the composite endpoint. Conversely, there was no significant association between negative outcomes on the exercise test and the occurrence of a device-delivered electric shock. (4) Conclusions: The exercise test performed at the time of ICD implantation do not predict the occurrence of device-delivered electric shock. The exercise test and the first electric shock are two independent markers of poor prognosis. Full article

Background: We evaluated the outcome of PCI of de novo stenosis with drug-coated balloons (DCB) versus drug-eluting stents (DES) in patients with insulin-treated diabetes mellitus (ITDM) versus non-insulin-treated diabetes mellitus (NITDM). Methods: Patients were randomized in the BASKET-SMALL 2 trial to DCB or DES and followed over 3 years for MACE (cardiac death, non-fatal myocardial infarction [MI], and target vessel revascularization [TVR]). Outcome in the diabetic subgroup (n = 252) was analyzed with respect to ITDM or NITDM. Results: In NITDM patients (n = 157), rates of MACE (16.7% vs. 21.9%, hazard ratio [HR] 0.68, 95% confidence interval [CI] 0.29–1.58, p = 0.37), death, non-fatal MI, and TVR (8.4% vs. 14.5%, HR 0.30, 95% CI 0.09–1.03, p = 0.057) were similar between DCB and DES. In ITDM patients (n = 95), rates of MACE (DCB 23.4% vs. DES 22.7%, HR 1.12, 95% CI 0.46–2.74, p = 0.81), death, non-fatal MI, and TVR (10.1% vs. 15.7%, HR 0.64, 95% CI 0.18–2.27, p = 0.49) were similar between DCB and DES. TVR was significantly lower with DCB versus DES in all diabetic patients (HR 0.41, 95% CI 0.18–0.95, p = 0.038). Conclusions: DCB compared to DES for treatment of de novo coronary lesions in diabetic patients was associated with similar rates of MACE and numerically lower need for TVR both for ITDM and NITDM patients. Full article

Background: Although several studies suggest that heparins prevent arrhythmias caused by acute myocardial infarction (AMI), the molecular mechanisms involved remain unclear. To investigate the involvement of pharmacological modulation of adenosine (ADO) signaling in cardiac cells by a low-molecular weight heparin (enoxaparin; ENOX) used in AMI therapy, the effects of ENOX on the incidences of ventricular arrhythmias (VA), atrioventricular block (AVB), and lethality (LET) induced by cardiac ischemia and reperfusion (CIR) were evaluated, with or without ADO signaling blockers. Methods: To induce CIR, adult male Wistar rats were anesthetized and subjected to CIR. Electrocardiogram (ECG) analysis was used to evaluate CIR-induced VA, AVB, and LET incidence, after treatment with ENOX. ENOX effects were evaluated in the absence or presence of an ADO A1-receptor antagonist (DPCPX) and/or an inhibitor of ABC transporter-mediated cAMP efflux (probenecid, PROB). Results: VA incidence was similar between ENOX-treated (66%) and control rats (83%), but AVB (from 83% to 33%) and LET (from 75% to 25%) incidences were significantly lower in rats treated with ENOX. These cardioprotective effects were blocked by either PROB or DPCPX. Conclusion: These results indicate that ENOX was effective in preventing severe and lethal arrhythmias induced by CIR due to pharmacological modulation of ADO signaling in cardiac cells, suggesting that this cardioprotective strategy could be promising in AMI therapy. Full article

Sodium glucose cotransporter 2 inhibitor (SGLT2i) is a class of drugs that were originally intended for decreasing blood glucose in diabetes. However, recent trials have shown that there are other beneficial effects. Major clinical trials involving SGLT2i medications from 2015 to 2022 were reviewed using PUBMED search. Recent major SGLT2i landmark trials have demonstrated benefits for cardiovascular disease (reduce major adverse cardiovascular events (heart attack, stroke, cardiovascular death), hospitalization for heart failure, all-cause death), and renal disease (delay the onset of dialysis) regardless of diabetic status. The consistent cardiorenal benefits observed in major landmark trials have resulted in the rapid adoption of SGLT2i therapy not only in diabetes guidelines but also cardiovascular and renal guidelines. Full article