Mitochondrial Heteroplasmy as a Marker for Premature Coronary Artery Disease: Analysis of the Poly-C Tract of the Control Region Sequence.

Mitochondrial DNA (mtDNA) differs from the nuclear genome in many aspects: a maternal inheritance pattern; being more prone to acquire somatic de novo mutations, accumulative with age; and the possible coexistence of different mtDNA alleles (heteroplasmy). Mitochondria are key cellular organelles responsible for energy production and involved in complex mechanisms, including atherosclerosis. In this scenario, we aimed to evaluate mtDNA variants that could be associated with premature cardiovascular disease. We evaluated 188 consecutive patients presenting with premature myocardial infarction with ST elevation (STEMI) confirmed by coronary angiogram. mtDNA polymorphisms and clinical data were evaluated and compared with 271 individuals from the same population (control group). Tobacco consumption (80.85% vs. 21.21%, p < 0.01) and dyslipidemia (38.83% vs. 28.41%, p = 0.02) were significantly more frequent among STEMI patients. Moreover, C16223T mtDNA mutation and poly-C heteroplasmy were significantly more frequent among premature STEMI male patients than in controls. The OR associated C16223T mtDNA with the increased presence of cardiovascular risk factors. Our data suggest that mtDNA 16223T and heteroplasmy may be associated with unstable premature atherosclerosis disease in men. Moreover, the presence of cardiovascular risk factors (CVRFs) was associated with C16223T mtDNA, with a cumulative effect. Protective mitochondrial pathways are potential therapeutic targets. Preventing exposure to the damaging mechanisms associated with CVRFs is of utmost importance.

Association of the Surgical Technique With the Structural Valve Deterioration of a Bioprosthesis: A Prospective Cohort Study.

The Trifecta aortic valve is a prosthesis with externally mounted leaflets and a stent which may be deformed during implant. Our aim was to know if the use of the holder as a protection device during the knotting has an impact on the incidence of structural valve deterioration (SVD) or endocarditis. Prospective cohort study where all patients who underwent aortic valve replacement with a Trifecta aortic valve between 2013 and 2018 were included. The use of the holder as a protection device was collected in a database. Propensity-score matched methods were used and analyses were based on competing events. Death without SVD or prosthesis replacement not due to SVD was considered competing events. 782 patients were included, 352 pairs after the matching. Rates of SVD at 5 and 8 years were 5.8% (95% CI 3.5-8.7) and 13.6% (95% CI 9.2-18.9) in the group without holder and 2.3% (95% CI 1-4.5) and 7% (95% CI 4.2-10.8) in the group with holder; sHR = 0.49 (95% CI 0.27-0.86; P = 0.015). The risk of endocarditis at 8 years was 4.8% (95% CI 2.8-7.4) in the group without holder and 2.3% (95% CI 1.1-4.3) in the group with holder, sHR = 0.49 (95% CI 0.21-1.15, P = 0.1). The use of holder as a protection device during the knotting of the Trifecta aortic valve is associated with less risk of SVD.

Transcatheter tricuspid valve interventions: Current status and future perspectives.

The development of transcatheter therapies to treat valvular heart diseases has changed the rules of the game, particularly in the case of aortic stenosis and mitral regurgitation. In the last years, the tricuspid valve has also been the focus of these percutaneous techniques for several reasons: (1) tricuspid regurgitation is a frequent disease associated with poor clinical outcomes in spite of medical treatment, leading to end-stage right ventricular heart failure, (2) surgical tricuspid valve repair or replacement has been the treatment of choice for patients with tricuspid valve disease, but high mortality rates for isolated surgical tricuspid valve intervention have been reported in the literature, and (3) most patients with tricuspid pathology are ultimately denied cardiac surgery because of their comorbidity burden. Thus, in this context the development of less invasive catheter-based therapies would be of high clinical relevance. The present review provides an overview regarding the framework of chronic tricuspid regurgitation transcatheter therapeutic options, summarizes the transcatheter systems under clinical use or clinical evaluation with their technical features, and describes the updated current evidence in this challenging and evolving field.

6-Month Outcomes of the TricValve System in Patients With Tricuspid Regurgitation: The TRICUS EURO Study.

BACKGROUND: Severe tricuspid regurgitation (TR) is frequently associated with significant morbidity and mortality; such patients are often deemed to be at high surgical risk. Heterotopic bicaval stenting is an emerging, attractive transcatheter solution for these patients. OBJECTIVES: The aim of this study was to evaluate the 30-day safety and 6-month efficacy outcomes of specifically designed bioprosthetic valves for the superior and inferior vena cava. METHODS: TRICUS EURO (Safety and Efficacy of the TricValve® Transcatheter Bicaval Valves System in the Superior and Inferior Vena Cava in Patients With Severe Tricuspid Regurgitation) is a nonblinded, nonrandomized, single-arm, multicenter, prospective trial that enrolled patients from 12 European centers between December 2019 and February 2021. High-risk individuals with severe symptomatic TR despite optimal medical therapy were included. The primary endpoint was quality-of-life (QOL) improvement measured by Kansas City Cardiomyopathy Questionnaire score and New York Heart Association (NYHA) functional class improvement at 6-month follow-up. RESULTS: Thirty-five patients (mean age 76 ± 6.8 years, 83% women) were treated using the TricValve system. All patients at baseline were in NYHA functional class III or IV. At 30 days, procedural success was 94%, with no procedural deaths or conversions to surgery. A significant increase in QOL at 6 months follow-up was observed (baseline and 6-month Kansas City Cardiomyopathy Questionnaire scores 42.01 ± 22.3 and 59.7 ± 23.6, respectively; P = 0.004), correlating with a significant improvement in NYHA functional class, with 79.4% of patients noted to be in functional class I or II at 6 months (P = 0.0006). The rates of 6-month all-cause mortality and heart failure hospitalization were 8.5% and 20%, respectively. CONCLUSIONS: The dedicated bicaval system for treating severe symptomatic TR was associated with a high procedural success rate and significant improvements in both QOL and functional classification at 6 months follow-up.

Transcatheter Versus Surgical Aortic Valve Replacement in Patients With Complex Coronary Artery Disease.

OBJECTIVES: The aim of this study was to compare, in a cohort of patients with complex coronary artery disease (CAD) and severe aortic stenosis (AS), the clinical outcomes associated with transfemoral transcatheter aortic valve replacement (TAVR) (plus percutaneous coronary intervention [PCI]) versus surgical aortic valve replacement (SAVR) (plus coronary artery bypass grafting [CABG]). BACKGROUND: Patients with complex CAD were excluded from the main randomized trials comparing TAVR with SAVR, and no data exist comparing TAVR + PCI vs SAVR + CABG in such patients. METHODS: A multicenter study was conducted including consecutive patients with severe AS and complex CAD (SYNTAX [Synergy Between PCI with Taxus and Cardiac Surgery] score >22 or unprotected left main disease). A 1:1 propensity-matched analysis was performed to account for unbalanced covariates. The rates of major adverse cardiac and cerebrovascular events (MACCE), including all-cause mortality, nonprocedural myocardial infarction, need for new coronary revascularization, and stroke, were evaluated. RESULTS: A total of 800 patients (598 undergoing SAVR + CABG and 202 undergoing transfemoral TAVR + PCI) were included, and after propensity matching, a total of 156 pairs of patients were generated. After a median follow-up period of 3 years (interquartile range: 1-6 years), there were no significant differences between groups for MACCE (HR for transfemoral TAVR vs SAVR: 1.33; 95% CI: 0.89-1.98), all-cause mortality (HR: 1.25; 95% CI: 0.81-1.94), myocardial infarction (HR: 1.16; 95% CI: 0.41-3.27), and stroke (HR: 0.42; 95% CI: 0.13-1.32), but there was a higher rate of new coronary revascularization in the TAVR + PCI group (HR: 5.38; 95% CI: 1.73-16.7). CONCLUSIONS: In patients with severe AS and complex CAD, TAVR + PCI and SAVR + CABG were associated with similar rates of MACCE after a median follow-up period of 3 years, but TAVR + PCI recipients exhibited a higher risk for repeat coronary revascularization. Future trials are warranted.

Evaluation of cardiovascular events in patients with hepatocellular carcinoma treated with sorafenib in the clinical practice. The CARDIO-SOR study.

BACKGROUND AND AIMS: The effectiveness of systemic treatment in advanced hepatocellular carcinoma (HCC) depends on the selection of patients, management of cirrhosis complications and expertise to treat adverse events. The aims of the study are to assess the frequency and management of cardiovascular events in HCC patients treated with sorafenib (SOR) and to create a scale to predict the onset of major adverse cardiovascular events (MACE). METHOD: Observational retrospective study with consecutive HCC patients treated with SOR between 2007 and 2019 in a western centre. In order to classify cardiovascular risk pre-SOR, we designed the CARDIOSOR scale with age, hypertension, diabetes, dyslipidaemia and peripheral vascular disease. Other adverse events, dosing and outcome data were collected during a homogeneous protocolled follow-up. RESULTS: Two hundred ninety-nine patients were included (219 BCLC-C). The median overall survival was 11.1 months (IQR 5.6-20.5), and duration of treatment was 7.4 months (IQR 3.3-14.7). Seventeen patients (6%) stopped SOR due to cardiovascular event. Thirty-three patients suffered MACE (7 heart failure, 11 acute coronary syndrome, 12 cerebrovascular accident and 8 peripheral vascular ischemia); 99 had a minor cardiovascular event, mainly hypertension (n = 81). Age was the only independent factor associated to MACE (HR 1.07; 95% CI 1.03-1.12; P = .002). The CARDIOSOR scale allows to identify the group of patients with higher risk of MACE (sHR 3.4; 95% CI 1.4-6.7; P = .04). CONCLUSION: The incidence of cardiovascular events in HCC patients treated with SOR is higher than expected. Multidisciplinary approach and clinical tools like CARDIOSOR scale could be helpful to manage these patients.

Premature STEMI in Men and Women: Current Clinical Features and Improvements in Management and Prognosis.

Background: Coronary artery disease (CAD) is the most frequent cause of ST-segment elevation myocardial infarction (STEMI). Etiopathogenic and prognostic characteristics in young patients may differ from older patients and young women may present worse outcomes than men. We aimed to evaluate the clinical characteristics and prognosis of men and women with premature STEMI. METHODS: A total 1404 consecutive patients were referred to our institution for emergency cardiac catheterization due to STEMI suspicion (1 January 2014-31 December 2018). Patients with confirmed premature (<55 years old in men and <60 in women) STEMI (366 patients, 83% men and 17% women) were included (359 atherothrombotic and 7 spontaneous coronary artery dissection (SCAD)). RESULTS: Premature STEMI patients had a high prevalence of classical cardiovascular risk factors. Mean follow-up was 4.1 years (±1.75 SD). Mortality rates, re-hospitalization, and hospital stay showed no significant differences between sexes. More than 10% of women with premature STEMI suffered SCAD. There were no significant differences between sexes, neither among cholesterol levels nor in hypolipemiant therapy. The global survival rates were similar to that expected in the general population of the same sex and age in our region with a significantly higher excess of mortality at 6 years among men compared with the general population. CONCLUSION: Our results showed a high incidence of cardiovascular risk factors, a high prevalence of SCAD among young women, and a generally good prognosis after standardized treatment. During follow-up, 23% suffered a major cardiovascular event (MACE), without significant differences between sexes and observed survival at 1, 3, and 6 years of follow-up was 96.57% (95% CI 94.04-98.04), 95.64% (95% CI 92.87-97.35), and 94.5% (95% CI 91.12-97.66). An extra effort to prevent/delay STEMI should be invested focusing on smoking avoidance and optimal hypolipemiant treatment both in primary and secondary prevention.

Survival After Thoracoscopic Surgery or Open Lobectomy: Systematic Review and Meta-Analysis.

BACKGROUND: Video-assisted thoracoscopic surgery (VATS) has been shown to reduce hospital stays and pain compared with open lobectomy to treat non-small cell lung cancer. Because of the low rate of deaths, it is difficult to show differences in survival in individual studies. The objective of this study was to compare short- and long-term mortality by means of a systematic review and meta-analysis. METHODS: The reviewers systematically searched studies that compared VATS vs open lobectomy and provided data on 30-day mortality or long-term survival (>5 years). For long-term outcomes, studies included patients with the same cancer stage or, if several stages were included, the studies had to control for cancer stage in their propensity score model. A pooled odds ratio and hazard ratio (HR) was respectively calculated for short- and long-term outcomes. RESULTS: A total of 33 works were identified, comprising 61,633 patients. VATS led to lower postoperative mortality (odds ratio, 0.64; 95% confidence interval [CI], 0.56 to 0.73) and higher long-term survival (HR, .88; 95% CI, 0.81 to 0.96). Disease-free survival was similar in both groups (HR, 0.94; 95% CI, 0.80 to 1.10). CONCLUSIONS: For non-small cell lung cancer treated with lobectomy, VATS was associated with lower postoperative mortality and greater long-term survival compared with open lobectomy. Disease-free survival was similar between both groups.

Familial Hypercholesterolemia in Premature Acute Coronary Syndrome. Insights from CholeSTEMI Registry.

Familial hypercholesterolemia (FH) is an underdiagnosed genetic inherited condition that may lead to premature coronary artery disease (CAD). FH has an estimated prevalence in the general population of about 1:313. However, its prevalence in patients with premature STEMI (ST-elevation myocardial infarction) has not been widely studied. This study aimed to evaluate the prevalence of FH in patients with premature STEMI. Cardiovascular risk factors, LDLc (low-density lipoprotein cholesterol) evolution, and differences between genders were also evaluated. Consecutive patients were referred for cardiac catheterization to our center due to STEMI suspicion in 2018. From the 80 patients with confirmed premature CAD (men < 55 and women < 60 years old with confirmed CAD), 56 (48 men and eight women) accepted to be NGS sequenced for the main FH genes. Clinical information and DLCN (Dutch Lipid Clinic Network) score were analyzed. Only one male patient had probable FH (6-7 points) and no one reached a clinically definite diagnosis. Genetic testing confirmed that the only patient with a DLCN score ≥6 has HF (1.8%). Smoking and high BMI the most frequent cardiovascular risk factors (>80%). Despite high doses of statins being expected to reduce LDLc levels at STEMI to current dyslipidemia guidelines LDL targets (<55 mg/dL), LDLc control levels were out of range. Although still 5.4 times higher than in general population, the prevalence of FH in premature CAD is still low (1.8%). To improve the genetic yield, genetic screening may be considered among patients with probable or definite FH according to clinical criteria. The classical cardiovascular risk factors prevalence far exceeds FH prevalence in patients with premature STEMI. LDLc control levels after STEMI were out range, despite intensive hypolipemiant treatment. These findings reinforce the need for more aggressive preventive strategies in the young and for intensive lipid-lowering therapy in secondary prevention.

Long term follow up of percutaneous treatment for degenerated Mitroflow prosthesis with self-expanding transcatheter aortic valve implantation.

BACKGROUND: The durability of aortic valve bioprosthesis and the structural valve deterioration (SVD) are could be treated with valve-in-valve (VIV) transcatheter aortic valve implantation (TAVI). This technique has been proven to be a feasible procedure with good results in selected patients. The aim of this work was to assess the long-term results of this TAVI with an autoexpandable valve in patients with failed Mitroflow (MF) bioprosthetic aortic valves. METHODS: Single center, observational and prospective study that included 65 consecutive patients with symptomatic failed MF bioprosthetic aortic valve, treated with VIV-TAVI. The primary endpoints were clinical long-term events including all-cause mortality, cardiovascular mortality, re-hospitalization due to heart failure, stroke/transient ischemic attack (TIA) and endocarditis. Secondary endpoints were the absence of SVD or patient-prosthesis mismatch (PPM) and valve hemodynamics analysis at follow-up. RESULTS: Between March 2012 to July 2019, 65 symptomatic patients (age 80.4±5.9 years) with degenerated MF valves (numbers 19: 27.7%; 21: 38.5%; 23: 21.5%; 25: 12.3%) underwent CoreValve (n=11) or Evolut R (n=54) implantation (23, 26 and 29 mm sizes). The STS predicted risk of mortality was 6.39%±5.62%. The primary combined endpoint occurred in 32.3% of the cases. A total of 13 patients (20%) died during follow-up, but 4 (7.3%) from cardiovascular causes. Two patients were reported of having a stroke/TIA and 5 readmissions for cardiovascular causes were reported (2 of them within the first 30 days). Twenty-five patients (38.5%) presented PPM during follow-up, being PPM severe in 15 (23.1%). CONCLUSIONS: Self-expanding TAVI for degenerated MF bioprosthesis has favourable long-term outcomes. It is a good option in order to avoid the risks of redo surgery in selected patients.

IL17RA in early-onset coronary artery disease: Total leukocyte transcript analysis and promoter polymorphism (rs4819554) association.

BACKGROUND AND AIMS: The interleukin-17 (IL-17) pathway would play an important role in the pathogenesis of atherosclerosis and coronary-artery disease (CAD). The IL-17 inflammatory mediators are expressed by Th17 cells, a group of CD4 + leukocytes that infiltrate the vascular milieu and are pivotal in the origin, progression, stability and rupture of the atherosclerotic lesion. Cigarette smoke compounds stimulated the expression of IL-17 and IL-17-receptors. In atherogenic mice models the deficiency of IL-17RA resulted in a reduction of the atherosclerotic lesion size and leukocyte infiltrate. We hypothesised that common the IL-17RA transcript might be differential expressed in the leukocytes from CAD patients and healthy individuals. METHODS: The relative amount of the IL-17RA to ACTB transcript was determined in total leukocytes of 55 patients and 50 controls, all smokers. We genotyped the IL-17RA rs48195554 promoter polymorphisms in 390 healthy controls and 450 early-onset CAD patients. RESULTS: Patients showed significantly higher mean IL-17RA normalised transcript value than controls (p < 0.001). For the IL-17RA rs48195554 promoter polymorphisms, IL-17RA G-carriers showed higher transcript values. However, allele and genotype frequencies did not differ between patients and controls and we thus excluded a significant association with CAD. CONCLUSIONS: The higher levels of the IL-17RA transcript among CAD-patients was in agreement with a role for the IL-17 pathway in the pathogenesis of coronary atherosclerosis.

Impact of Saharan dust exposure on airway inflammation in patients with ischemic heart disease.

Epidemiological studies found that increases in the concentrations of airborne particulate matter (PM) smaller than 10 microns diameter (PM10) in the ambient air due to desert dust outbreaks contribute to global burden of diseases, primarily as a result of increased risk of cardiovascular morbidity and mortality. No studies have investigated the possible association between desert dust inhalation and airway inflammation in patients with ischemic heart disease (IHD). Induced sputum was collected in 38 patients and analyzed to determine markers of airway inflammation (Transforming Growth Factor-ß1 [TGF-ß1] and hydroxyproline) concentrations. For the purpose of the investigation, PM10 and reactive gases concentrations measured in the European Air Quality Network implemented in the Canary Islands were also used. We identified Saharan desert dust using meteorology and dust models. Patients affected by smoking, chronic obstructive pulmonary disease (COPD), asthma, pulmonary abnormalities, acute bronchial or pulmonary disease were excluded. The median of age of patients was 64.71 years (56.35-71.54) and 14 (38.84%) of them were women. TGF-ß1 and hydroxyproline in sputum were highly associated to PM10 inhalation from the Saharan desert. According to a regression model, an increase of 1 µg/m3 of PM10 concentrations due to desert dust, results in an increase of 3.84 pg/gwt of TGF-ß1 (R2 adjusted = 89.69%) and of 0.80 µg/gwt of hydroxyproline (R2 adjusted = 85.28%) in the sputum of patients. The results of this study indicate that the exposure to high PM10 concentrations due to Saharan dust events are associated with intense inflammatory reaction in the airway mucosae of IHD-patients.

Life Expectancy after Surgery for Ascending Aortic Aneurysm.

Introduction: The life expectancy of patients who undergo ascending aortic replacement is unknown. The life expectancy of a population depends on a collection of environmental and socio-economic factors of the territory where they reside. Our aim was to compare the life expectancy of patients undergoing surgery for ascending aortic aneurysm with that of the general population matching by age, sex, and territory. In addition, we aimed to know the late complications, causes of death and risk factors. Methods: All patients who underwent elective replacement of an ascending aortic aneurysm at our institution between 2000 and 2019 were included. The long-term survival of the sample was compared with that of the general population using data of the National Institute of Statistics. Results: For patients who survived the postoperative period, observed cumulative survival at three, five and eight years was 94.07% (95% CI 91.87%-95.70%), 89.96% (95% CI 86.92%-92.33%) and 82.72% (95% CI 77.68%-86.71%). Cumulative survival of the general population at three, five and eight years was 93.22%, 88.30%, and 80.27%. Cancer and cardiac failure were the main causes of death. Conclusions: Long-term survival of patients undergoing elective surgery for ascending aortic aneurysm who survive the postoperative period completely recover their life expectancy.

Life expectancy of patients undergoing surgical aortic valve replacement compared with that of the general population.

OBJECTIVES: Surgical aortic valve replacement (SAVR) changes the natural history of severe aortic stenosis. However, whether the life expectancy of patients with severe aortic stenosis undergoing this surgical procedure is fully restored is unknown. The objective of this study was to assess if the life expectancy of patients aged >75 years is fully restored after undergoing surgery for severe aortic stenosis. METHODS: We compared long-term survival of a group of patients aged >75 years, who underwent SAVR at our institution with the long-term survival of the general population. We matched each patient with 100 simulated individuals (control group) of the same age, sex and geographical region who died as indicated by the National Institute of Statistics. We compared survival curves and calculated hazard ratio (HR) or incidence rate ratio. Statistical significance existed if confidence intervals (CIs) did not overlap or did not include the value 1, as appropriate. RESULTS: Average life expectancy of surgical patients who survived the postoperative period was 90.91 months (95% CI 82.99-97.22), compared to 92.94 months (95% CI 92.39-93.55) in the control group. One-, 5- and 8-year survival rates for SAVR patients who were discharged from the hospital were 94.9% (95% CI 92.74-96.43%), 71.66% (95% CI 67.37-75.5%) and 44.48% (95% CI 38.14-50.61%), respectively, compared to that of the general population: 95.8% (95% CI 95.64-95.95%), 70.64% (95% CI 70.28%-71%) and 47.91% (95% CI 47.52-48.31%), respectively (HR 1.07, 95% CI 0.94-1.22). CONCLUSION: For patients over the age of 75 years who underwent SAVR and survived the postoperative period, life expectancy and survival rates were similar to that of the general population.

Cerebral protection devices for transcatheter aortic valve replacement.

Aortic stenosis is the most prevalent primary valve disease in developed countries. Its prevalence is increasing due to population aging. Transcatheter aortic valve replacement (TAVR) is a sterling therapy for symptomatic patients with severe aortic stenosis and high or intermediate surgery risk. The number of procedures has increased exponentially expanding to younger and lower risk patients. Despite new-generation TAVR devices and enhanced operator skills, cerebrovascular events (CVEs) carry on being one of the most severe complications, increasing morbi-mortality. CVE might be under reported because there are few studies with rigorous neurological clinical assessment. Several imaging studies show most of CVE after TAVR has a probable embolic etiology. The risk of CVE ranges from 2.7% to 5.5% at 30 days. As TAVR expands to younger and lower risk patients, the prevention of stroke plays an increasingly important role. Cerebral protection devices (CPD) were designed to reduce the risk of CVE during TAVR. This review describes the scientific evidence on CVE after TAVR and summarizes the performance and results of the main CPDs.