Atrial Fibrillation, Atrial Myopathy, and Thromboembolism: The Additive Value of Echocardiography and Possible New Horizons for Risk Stratification.

Atrial fibrillation (AF) is the most common cardiac sustained arrhythmia, and it is associated with increased stroke and dementia risk. While the established paradigm attributes these complications to blood stasis within the atria and subsequent thrombus formation with cerebral embolization, recent evidence suggests that atrial myopathy (AM) may play a key role. AM is characterized by structural and functional abnormalities of the atria, and can occur with or without AF. Moving beyond classifications based solely on episode duration, the 4S-AF characterization has offered a more comprehensive approach, incorporating patient's stroke risk, symptom severity, AF burden, and substrate assessment (including AM) for tailored treatment decisions. The "ABC" pathway emphasizes anticoagulation, symptom control, and cardiovascular risk modification and emerging evidence suggests broader benefits of early rhythm control strategies, potentially reducing stroke and dementia risk and improving clinical outcomes. However, a better integration of AM assessment into the current framework holds promise for further personalizing AF management and optimizing patient outcomes. This review explores the emerging concept of AM and its potential role as a risk factor for stroke and dementia and in AF patients' management strategies, highlighting the limitations of current risk stratification methods, like the CHA2DS2-VASc score. Echocardiography, particularly left atrial (LA) strain analysis, has shown to be a promising non-invasive tool for AM evaluation and recent studies suggest that LA strain analysis may be a more sensitive risk stratifier for thromboembolic events than AF itself, with some studies showing a stronger association between LA strain and thromboembolic events compared to traditional risk factors. Integrating it into routine clinical practice could improve patient management and targeted therapies for AF and potentially other thromboembolic events. Future studies are needed to explore the efficacy and safety of anticoagulation in AM patients with and without AF and to refine the diagnostic criteria for AM.

One-Month DAPT Reduces Major Bleeding Compared with Longer Term Treatment without Excess Stent Thrombosis: a Systematic Review and Meta-analysis of Randomized Clinical Trials.

Dual antiplatelet therapy (DAPT) remains the gold standard in patients undergoing percutaneous coronary intervention (PCI). The aim of this meta-analysis is to evaluate the clinical safety of 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor, after PCI with drug eluting stents (DES). PubMed, MEDLINE, Embase, Scopus, Google Scholar, CENTRAL and ClinicalTrials.gov databases search identified 5 RCTs with 29,831 patients who underwent PCI with DES and compared 1-month versus >1-month DAPT. The primary endpoint was major bleeding and co-primary endpoint stent thrombosis. The secondary endpoint included all-cause mortality, cardiovascular death, myocardial infarction (MI), stroke and major adverse cardiovascular or cerebrovascular events (MACCE). Compared to >1-month DAPT, the 1-month DAPT was associated with lower rate of major bleeding (OR=0.66, 95%CI: 0.45 to 0.97, p=0.03, I2=71%), whereas stent thrombosis had similar rate in both study groups (OR=1.08, 95%CI: 0.81 to 1.44, p=0.60, I2=0.0%). The study groups had similar risk for all-cause mortality (OR=0.89, 95%CI: 0.77 to 1.04, p=0.14, I2=0.0%), CV death (OR=0.84, 95%CI: 0.59 to 1.19, p=0.32, I2=0.0%), MI (OR=1.04, 95%CI: 0.89 to 1.21, p=0.62, I2=0.0%) and stroke (OR=0.82, 95%CI: 0.64 to 1.05, p=0.11, I2=6%). The risk of MACCE was lower (OR=0.86, 95%CI: 0.76 to 0.97, p=0.02, I2=25%) in the 1-month DAPT compared to >1-month DAPT. In conclusion, in patients undergoing PCI with DES, 1-month DAPT followed by aspirin or a P2Y12 receptor inhibitor reduce major bleeding with no risk of increased thrombotic risk compared to longer term DAPT.

Myocardial Work Indices Predict Hospitalization in Patients with Advanced Heart Failure.

BACKGROUND: An increasing proportion of heart failure (HF) patients progress to the advanced stage (AdHF) with high event rates and limited treatment options. Echocardiography, particularly Speckle Tracking-derived myocardial work (MW), is useful for HF diagnosis and prognosis. We aimed to assess MW's feasibility in the prognostic stratification of AdHF. METHODS: We retrospectively screened patients with AdHF who accessed our hospital in 2018-2022. We excluded subjects with inadequate acoustic windows; unavailable brachial artery cuff pressure at the time of the echocardiography; atrial fibrillation; and mitral or aortic regurgitation. We measured standard parameters and left ventricular (LV) strain (LS) and MW. The population was followed up to determine the composite outcomes of all-cause mortality, left ventricular assist device implantation and heart transplantation (primary endpoint), as well as unplanned HF hospitalization (secondary endpoint). RESULTS: We enrolled 138 patients, prevalently males (79.7%), with a median age of 58 years (IQR 50-62). AdHF etiology was predominantly non-ischemic (65.9%). Thirty-five patients developed a composite event during a median follow-up of 636 days (IQR 323-868). Diastolic function, pulmonary pressures, and LV GLS and LV MW indices were not associated with major events. Contrarily, for the secondary endpoint, the hazard ratio for each increase in global work index (GWI) by 50 mmHg% was 0.90 (p = 0.025) and for each increase in global constructive work (GCW) by 50 mmHg% was 0.90 (p = 0.022). Kaplan-Meier demonstrated better endpoint-free survival, with an LV GWI ≥ 369 mmHg%. CONCLUSIONS: GWI and GCW, with good feasibility, can help in the better characterization of patients with AdHF at higher risk of HF hospitalization and adverse events, identifying the need for closer follow-up or additional HF therapy.

New perspectives in the echocardiographic hemodynamics multiparametric assessment of patients with heart failure.

International Guidelines consider left ventricular ejection fraction (LVEF) as an important parameter to categorize patients with heart failure (HF) and to define recommended treatments in clinical practice. However, LVEF has some technical and clinical limitations, being derived from geometric assumptions and is unable to evaluate intrinsic myocardial function and LV filling pressure (LVFP). Moreover, it has been shown to fail to predict clinical outcome in patients with end-stage HF. The analysis of LV antegrade flow derived from pulsed-wave Doppler (stroke volume index, stroke distance, cardiac output, and cardiac index) and non-invasive evaluation of LVFP have demonstrated some advantages and prognostic implications in HF patients. Speckle tracking echocardiography (STE) is able to unmask intrinsic myocardial systolic dysfunction in HF patients, particularly in those with LV preserved EF, hence allowing analysis of LV, right ventricular and left atrial (LA) intrinsic myocardial function (global peak atrial LS, (PALS)). Global PALS has been proven a reliable index of LVFP which could fill the gaps "gray zone" in the previous Guidelines algorithm for the assessment of LV diastolic dysfunction and LVFP, being added to the latest European Association of Cardiovascular Imaging Consensus document for the use of multimodality imaging in evaluating HFpEF. The aim of this review is to highlight the importance of the hemodynamics multiparametric approach of assessing myocardial function (from LVFP to stroke volume) in patients with HF, thus overcoming the limitations of LVEF.

Left ventricular ejection fraction: clinical, pathophysiological, and technical limitations.

Risk stratification of cardiovascular death and treatment strategies in patients with heart failure (HF), the optimal timing for valve replacement, and the selection of patients for implantable cardioverter defibrillators are based on an echocardiographic calculation of left ventricular ejection fraction (LVEF) in most guidelines. As a marker of systolic function, LVEF has important limitations being affected by loading conditions and cavity geometry, as well as image quality, thus impacting inter- and intra-observer measurement variability. LVEF is a product of shortening of the three components of myocardial fibres: longitudinal, circumferential, and oblique. It is therefore a marker of global ejection performance based on cavity volume changes, rather than directly reflecting myocardial contractile function, hence may be normal even when myofibril's systolic function is impaired. Sub-endocardial longitudinal fibers are the most sensitive layers to ischemia, so when dysfunctional, the circumferential fibers may compensate for it and maintain the overall LVEF. Likewise, in patients with HF, LVEF is used to stratify subgroups, an approach that has prognostic implications but without a direct relationship. HF is a dynamic disease that may worsen or improve over time according to the underlying pathology. Such dynamicity impacts LVEF and its use to guide treatment. The same applies to changes in LVEF following interventional procedures. In this review, we analyze the clinical, pathophysiological, and technical limitations of LVEF across a wide range of cardiovascular pathologies.

Left ventricular fibrosis as a main determinant of filling pressures and left atrial function in advanced heart failure.

AIMS: Advanced heart failure (AdHF) is characterized by variable degrees of left ventricular (LV) dysfunction, myocardial fibrosis, and raised filling pressures which lead to left atrial (LA) dilatation and cavity dysfunction. This study investigated the relationship between LA peak atrial longitudinal strain (PALS), assessed by speckle-tracking echocardiography (STE), and invasive measures of LV filling pressures and fibrosis in a group of AdHF patients undergoing heart transplantation (HTX). METHODS AND RESULTS: We consecutively enrolled patients with AdHF who underwent HTX at our Department. Demographic and basic echocardiographic data were registered, then invasive intracardiac pressures were obtained from right heart catheterization, and STE was also performed. After HTX, biopsy specimens from explanted hearts were collected to quantify the degree of LV myocardial fibrosis. Sixty-four patients were included in the study (mean age 62.5 ± 11 years, 42% female). The mean LV ejection fraction (LVEF) was 26.7 ± 6.1%, global PALS was 9.65 ± 4.5%, and mean pulmonary capillary wedge pressure (PCWP) was 18.8 ± 4.8 mmHg. Seventy-three % of patients proved to have severe LV fibrosis. Global PALS was inversely correlated with PCWP (R = -0.83; P < 0.0001) and with LV fibrosis severity (R = -0.78; P < 0.0001) but did not correlate with LVEF (R = 0.15; P = 0.2). Among echocardiographic indices of LV filling pressures, global PALS proved the strongest [area under the curve 0.955 (95% confidence interval 0.87-0.99)] predictor of raised (>18 mmHg) PCWP. CONCLUSION: In patients with AdHF, reduced global PALS strongly correlated with the invasively assessed LV filling pressure and degree of LV fibrosis. Such relationship could be used as non-invasive indicator for optimum patient stratification for therapeutic strategies.

Ventricular septal defect associated with aortic regurgitation and ascending aortic aneurysm: a case report.

INTRODUCTION: Ventricular septal defect (VSD) is one of the most common congenital cardiac anomalies. Patients with perimembranous VSD may have aortic regurgitation (AR) secondary to prolapse of the aortic cusp. CASE PRESENTATION: We present a case of 23-year-old White man with VSD, AR and ascending aortic aneurysm. The patient presented to outpatient clinic with weakness and gradual worsening shortness of breath for the past 5 years. Clinical examination revealed regular heart rhythm and loud continuous systolic-diastolic murmur (Lewin's grade 6/6), heard all over the precordium, associated with a palpable thrill. The ECG showed right axis deviation, fractionated QRS in V1 and signs of biventricular hypertrophy. The chest X-ray showed cardiomegaly. Transthoracic and transesophageal echocardiograms showed a perimembranous VSD with moderate restrictive shunt (Qp/Qs = 1.6), aortic regurgitation (AR), and ascending aortic aneurysm. Other clinical and laboratory findings were within normal limits. CONCLUSIONS: Perimembranous VSD, may be associated with aortic regurgitation and ascending aortic aneurysm as secondary phenomenon if it is not early diagnosed and successfully treated.

The association between daily step count and all-cause and cardiovascular mortality: a meta-analysis.

AIMS: There is good evidence showing that inactivity and walking minimal steps/day increase the risk of cardiovascular (CV) disease and general ill-health. The optimal number of steps and their role in health is, however, still unclear. Therefore, in this meta-analysis, we aimed to evaluate the relationship between step count and all-cause mortality and CV mortality. METHODS AND RESULTS: We systematically searched relevant electronic databases from inception until 12 June 2022. The main endpoints were all-cause mortality and CV mortality. An inverse-variance weighted random-effects model was used to calculate the number of steps/day and mortality. Seventeen cohort studies with a total of 226 889 participants (generally healthy or patients at CV risk) with a median follow-up 7.1 years were included in the meta-analysis. A 1000-step increment was associated with a 15% decreased risk of all-cause mortality [hazard ratio (HR) 0.85; 95% confidence interval (CI) 0.81-0.91; P < 0.001], while a 500-step increment was associated with a 7% decrease in CV mortality (HR 0.93; 95% CI 0.91-0.95; P < 0.001). Compared with the reference quartile with median steps/day 3867 (2500-6675), the Quartile 1 (Q1, median steps: 5537), Quartile 2 (Q2, median steps 7370), and Quartile 3 (Q3, median steps 11 529) were associated with lower risk for all-cause mortality (48, 55, and 67%, respectively; P < 0.05, for all). Similarly, compared with the lowest quartile of steps/day used as reference [median steps 2337, interquartile range 1596-4000), higher quartiles of steps/day (Q1 = 3982, Q2 = 6661, and Q3 = 10 413) were linearly associated with a reduced risk of CV mortality (16, 49, and 77%; P < 0.05, for all). Using a restricted cubic splines model, we observed a nonlinear dose-response association between step count and all-cause and CV mortality (Pnonlineraly < 0.001, for both) with a progressively lower risk of mortality with an increased step count. CONCLUSION: This meta-analysis demonstrates a significant inverse association between daily step count and all-cause mortality and CV mortality with more the better over the cut-off point of 3867 steps/day for all-cause mortality and only 2337 steps for CV mortality.

There is strong evidence showing that sedentary life may significantly increase the risk of cardiovascular (CV) disease and shorten the lifespan. However, the optimal number of steps, both the cut-off points over which we can see health benefits, and the upper limit (if any), and their role in health are still unclear. In this meta-analysis of 17 studies with almost 227 000 participants that assessed the health effects of physical activity expressed by walking measured in the number of steps, we showed that a 1000-step increment correlated with a significant reduction of all-cause mortality of 15%, and similarly, a 500-step increment correlated with a reduced risk of CV mortality of 7%. In addition, using the dose­response model, we observed a strong inverse nonlinear association between step count and all-cause mortality with significant differences between younger and older groups. It is the first analysis that not only looked at age and sex but also regional differences based on the weather zones, and for the first time, it assesses the effect of up to 20 000 steps/day on outcomes (confirming the more the better), which was missed in previous analyses. The analysis also revealed that depending on the outcomes, we do not need so many steps to have health benefits starting with even 2500/4000 steps/day, which, in fact, undermines the hitherto definition of a sedentary life.

Strain Rate Changes during Stress Echocardiography Are the Most Accurate Predictors of Significant Coronary Artery Disease in Patients with Previously Treated Acute Coronary Syndrome.

BACKGROUND AND AIMS: Dobutamine stress echocardiography (DSE) is a well-established non-invasive investigation for the detection of ischemic myocardial dysfunction. The aim of this study was to evaluate the accuracy of myocardial deformation parameters measured by speckle tracking echocardiography (STE) in predicting culprit coronary artery lesions in patients with prior revascularization and acute coronary syndrome (ACS). METHODS: We prospectively studied 33 patients with ischemic heart disease, a history of at least one episode of ACS and prior revascularization. All patients underwent a complete stress Doppler echocardiographic examination, including the myocardial deformation parameters of peak systolic strain (PSS), peak systolic strain rate (SR) and wall motion score index (WMSI). The regional PSS and SR were analyzed for different culprit lesions. RESULTS: The mean age of patients was 59 ± 11 years and 72.7% were males. At peak dobutamine stress, the change in regional PSS and SR in territories supplied by the LAD showed smaller increases compared to those in patients without culprit LAD lesions (p < 0.05 for all). Likewise, the regional parameters of myocardial deformation were reduced in patients with culprit LCx lesions compared to those with non-culprit LCx lesions and in patients with culprit RCA legions compared to those with non-culprit RCA lesions (p < 0.05 for all). In the multivariate analysis, the △ regional PSS (1.134 (CI = 1.059-3.315, p = 0.02)) and the △ regional SR (1.566 (CI = 1.191-9.013, p = 0.001)) for LAD territories predicted the presence of LAD lesions. Similarly, in a multivariable analysis, the △ regional PSS and the △SR predicted LCx culprit lesions and RCA culprit lesions (p < 0.05 for all). In an ROC analysis, the PSS and SR had higher accuracies compared to the regional WMSI in predicting culprit lesions. A △ regional SR of -0.24 for the LAD territories was 88% sensitive and 76% specific (AUC = 0.75; p < 0.001), a △ regional PSS of -1.20 was 78% sensitive and 71% specific (AUC = 0.76, p < 0.001) and a △ WMSI of -0.35 was 67% sensitive and 68% specific (AUC = 0.68, p = 0.02) in predicting LAD culprit lesions. Similarly, the △ SR for LCx and RCA territories had higher accuracies in predicting LCx and RCA culprit lesions. CONCLUSIONS: The myocardial deformation parameters, particularly the change in regional strain rate, are the most powerful predictors of culprit lesions. These findings strengthen the role of myocardial deformation in increasing the accuracy of DSE analyses in patients with prior cardiac events and revascularization.

Percutaneous Coronary Intervention Is Not Superior to Optimal Medical Therapy in Chronic Coronary Syndrome: A Meta-Analysis.

(1) Background and Aim: Conflicting evidence exists regarding the benefits of percutaneous coronary intervention (PCI) on survival and symptomatic relief of patients with chronic coronary syndrome (CCS) compared with optimal medical therapy (OMT). This meta-analysis is to evaluate the short- and long-term clinical benefit of PCI over and above OMT in CCS. (2) Methods: Main endpoints were major adverse cardiac events (MACEs), all-cause mortality, cardiovascular (CV) mortality, myocardial infarction (MI), urgent revascularization, stroke hospitalization, and quality of life (QoL). Clinical endpoints at very short (≤3 months), short- (<12 months), and long-term (≥ 12 months) follow-up were evaluated. (3) Results: Fifteen RCTs with a total of 16,443 patients with CCS (PCI n = 8307 and OMT n = 8136) were included in the meta-analysis. At mean follow-up of 27.7 months, the PCI group had similar risk of MACE (18.2 vs. 19.2 %; p < 0.32), all-cause mortality (7.09 vs. 7.88%; p = 0.56), CV mortality (8.74 vs. 9.87%; p = 0.30), MI (7.69 vs. 8.29%; p = 0.32), revascularization (11.2 vs. 18.3%; p = 0.08), stroke (2.18 vs. 1.41%; p = 0.10), and hospitalization for anginal symptoms (13.5 vs. 13.9%; p = 0.69) compared with OMT. These results were similar at short- and long-term follow-up. At the very short-term follow-up, PCI patients had greater improvement in the QoL including physical limitation, angina frequency, stability, and treatment satisfaction (p < 0.05 for all) but such benefits disappeared at the long-term follow-up. (4) Conclusions: PCI treatment of CCS does not provide any long-term clinical benefit compared with OMT. These results should have significant clinical implications in optimizing patient's selection for PCI treatment.

Role of cardiac and lung ultrasound in the COVID-19 era.

INTRODUCTION: The primary diagnostic method of Coronavirus disease 2019 is reverse transcription polymerase chain reaction of the nucleic acid of severe acute respiratory syndrome coronavirus 2 in nasopharyngeal swabs. There is growing evidence regarding the 2019 coronavirus disease imaging results on chest X-rays and computed tomography but the accessibility to standard diagnostic methods may be limited during the pandemic. EVIDENCE ACQUISITION: Databases used for the search were MEDLINE (PubMed), Scopus Search, and Cochrane Library. The research took into consideration studies published in English until March 2022 and was conducted using the following research query: ((((sars cov [MeSH Terms])) OR (COVID-19)) OR (Sars-Cov2)) OR (Coronavirus)) AND (((((2d echocardiography [MeSH Terms]) OR (doppler ultrasound imaging [MeSH Terms]))) OR (echography [MeSH Terms])) OR (LUS)) OR ("LUNG ULTRASOUND")). EVIDENCE SYNTHESIS: Pulmonary and cardiac ultrasound are cost-effective, widely available, and provide information that can influence management. CONCLUSIONS: Point-of-care ultrasonography is a method that can provide relevant clinical and therapeutic information in patients with COVID-19 where other diagnostic methods may not be easily accessible.

Acute pericarditis as a major clinical manifestation of long COVID-19 syndrome.

BACKGROUND: The long COVID-19 syndrome has been recently described and some reports have suggested that acute pericarditis represents important manifestation of long COVID-19 syndrome. The aim of this study was to identify the prevalence and clinical characteristics of patients with long COVID-19, presenting with acute pericarditis. METHODS: We retrospectively included 180 patients (median age 47 years, 62% female) previously diagnosed with COVID-19, exhibiting persistence or new-onset symptoms ≥12 weeks from a negative naso-pharyngeal SARS CoV2 swamp test. The original diagnosis of COVID-19 infection was determined by a positive swab. All patients had undergone a thorough physical examination. Patients with suspected heart involvement were referred to a complete cardiovascular evaluation. Echocardiography was performed based on clinical need and diagnosis of acute pericarditis was achieved according to current guidelines. RESULTS: Among the study population, shortness of breath/fatigue was reported in 52%, chest pain/discomfort in 34% and heart palpitations/arrhythmias in 37%. Diagnosis of acute pericarditis was made in 39 patients (22%). Mild-to-moderate pericardial effusion was reported in 12, while thickened and bright pericardial layers with small effusions (< 5 mm) with or without comet tails arising from the pericardium (pericardial B-lines) in 27. Heart palpitations/arrhythmias (OR:3.748, p = 0.0030), and autoimmune disease and allergic disorders (OR:4.147, p = 0.0073) were independently related to the diagnosis of acute pericarditis, with a borderline contribution of less likelihood of hospitalization during COVID-19 (OR: 0.100, p = 0.0512). CONCLUSION: Our findings suggest a high prevalence of acute pericarditis in patients with long COVID-19 syndrome. Autoimmune and allergic disorders, and palpitations/arrhythmias were frequently associated with pericardial disease.

Incidence and mortality of infective endocarditis in the last decade: a single center study.

BACKGROUND: Infective endocarditis (IE) is a significant disease characterized by high mortality and complications. The aim of this study was to evaluate the incidence/100 000 inhabitants and the in-hospital mortality/100 000 inhabitants of IE during the last 10 years in the province of Ravenna. METHODS AND RESULTS: We reviewed the public hospitals discharge database from January 2010 to December 2020 using the international classification of disease codification (ICD-9) for IE. We used the Italian national statistical institute (ISTAT) archive to estimate the number of Ravenna inhabitants/year. In 10 years, we identified a total of 407 patients with diagnosis of IE.The incidence of IE increased significantly from 6.29 cases/100 000 inhabitants in 2010 to 19.58 cases/100 000 inhabitants in 2020 ( P  < 0.001). Also, the in-hospital mortality from IE increased over the same number of years, from 1.8 deaths/100 000 inhabitants in 2010 to 4.4 deaths/100 000 inhabitants in 2020 ( P  < 0.001). The mortality rate (%) of IE over the years did not increase ( P = 0.565). Also, over the years there was no difference in the site of infection ( P  = 0.372), irrespective of the valve localization or type, native valve ( P  = 0.347) or prosthetic valve ( P  = 0.145). On logistic regression analysis, age was the only predictor of in-hospital mortality (odds ratio 1.045, 95% confidence interval: 1.015; 1.075, P  = 0.003). CONCLUSIONS: Ravenna-based data on IE showed increased disease incidence but unchanged mortality rate over 10 years of follow-up. Age remains the sole predictor of population-based mortality, irrespective of the nature of the valve, native or substitute, and the organism detected on microbiology.

Left Atrial Remodeling in Response to Aortic Valve Replacement: Pathophysiology and Myocardial Strain Analysis.

Severe aortic stenosis (AS) is the most common valve disease in the elderly and is associated with poor prognosis if treated only medically. AS causes chronic pressure overload, concentric left ventricular (LV) hypertrophy, myocardial stiffness, and diastolic dysfunction. This adverse remodeling also affects the left atrium (LA), which dilates and develops myocardial fibrosis, with a reduction in intrinsic function and a consequent high risk of the development of atrial fibrillation. Speckle-tracking echocardiography is able to detect myocardial dysfunction before other conventional parameters, such as LV ejection fraction, and also predict clinical outcomes. This review aims at describing LV and LA remodeling in AS and before and after aortic valve replacement and the usefulness of myocardial strain analysis in this clinical setting.

The Role of Inflammation in Cardiovascular Disease.

Atherosclerosis is a chronic inflammatory disease, in which the immune system has a prominent role in its development and progression. Inflammation-induced endothelial dysfunction results in an increased permeability to lipoproteins and their subendothelial accumulation, leukocyte recruitment, and platelets activation. Recruited monocytes differentiate into macrophages which develop pro- or anti-inflammatory properties according to their microenvironment. Atheroma progression or healing is determined by the balance between these functional phenotypes. Macrophages and smooth muscle cells secrete inflammatory cytokines including interleukins IL-1ß, IL-12, and IL-6. Within the arterial wall, low-density lipoprotein cholesterol undergoes an oxidation. Additionally, triglyceride-rich lipoproteins and remnant lipoproteins exert pro-inflammatory effects. Macrophages catabolize the oxidized lipoproteins and coalesce into a lipid-rich necrotic core, encapsulated by a collagen fibrous cap, leading to the formation of fibro-atheroma. In the conditions of chronic inflammation, macrophages exert a catabolic effect on the fibrous cap, resulting in a thin-cap fibro-atheroma which makes the plaque vulnerable. However, their morphology may change over time, shifting from high-risk lesions to more stable calcified plaques. In addition to conventional cardiovascular risk factors, an exposure to acute and chronic psychological stress may increase the risk of cardiovascular disease through inflammation mediated by an increased sympathetic output which results in the release of inflammatory cytokines. Inflammation is also the link between ageing and cardiovascular disease through increased clones of leukocytes in peripheral blood. Anti-inflammatory interventions specifically blocking the cytokine pathways reduce the risk of myocardial infarction and stroke, although they increase the risk of infections.

COVID-19 Prevention: Vitamin D Is Still a Valid Remedy.

Seven meta-analyses and systematic reviews and three later clinical trials argued that low vitamin D status increased susceptibility to COVID-19 and the risk of greater disease severity and mortality [...].

Left Ventricular Myocardial and Cavity Velocity Disturbances Are Powerful Predictors of Significant Coronary Artery Stenosis.

Background and Aim: Dobutamine stress echocardiography (DSE) is a well-established noninvasive investigation for significant coronary artery disease (CAD). The aim of this study was to evaluate the accuracy of cardiac Doppler parameters in predicting CAD. Methods: We prospectively studied 103 consecutive patients with suspected CAD based on typical symptoms; 59 proved to have CAD, and 44 patients proved to have no-CAD (n = 44). All patients underwent a complete stress Doppler echocardiographic examination. Total isovolumic time (T-IVT) as a marker of cavity dyssynchrony and wall motion score index (WMSI) were also calculated. Results: At peak dobutamine stress, the compromised LV longitudinal excursion (MAPSE), systolic septal and lateral velocities (s'), and diastolic indices were more pronounced in the CAD patients compared with those without CAD, but LV dimension did not differ between groups (p > 0.05). The WMSI was higher and t-IVT more prolonged in patients with CAD (p < 0.01 for both). Similarly, the changes were more pronounced in patients with significant CAD compared with insignificant CAD. On multivariate model, Δ mean s', OR 2.016 (1.610 to 3.190; p < 0.001), Δ E velocity OR 2.502 (1.179 to 1.108; p < 0.001), Δ t-IVT 2.206 (1.180 to 2.780; p < 0.001) and Δ WMSI OR 1.911 (1.401 to 3.001; p = 0.001) were the most powerful independent predictors of the presence of CAD, particularly when significant (>75%). Δ mean s' < 5.0 was 85% sensitive, 89% specific with AUC 0.92. Respective values for Δ E velocity <6.0 cm/s were 82%, 90% and 0.91; for Δ t-IVT > 4.5, 78%, 77% and 0.81 and for Δ FT ≥ 150 ms, 76%, 78% and 0.84 in predicating significant CAD. WMSI ≥ 0.7 was 75% sensitive, 77% specific with AUC of 0.81 in predicting significant CAD. The accuracy of DSE was higher in significant CAD compared to insignificant CAD (80% vs. 74%; p = 0.03). Conclusions: Compromised LV longitudinal systolic function, lower delta E wave, prolonged t-IVT, and increased WMSI were the most powerful independent predictors of the presence and significance of CAD. These finding strengthen the role of comprehensive DSE analysis in diagnosing ischemic disturbances secondary to significant CAD.

Left atrial myocardial intrinsic function remodeling response to repair of primary mitral regurgitation.

Severe mitral regurgitation (MR) is a common valve disease which is associated with high mortality, if only managed medically. MR produces chronic and progressive volume overload with left atrial (LA) and left ventricular (LV) dilatation and dysfunction, atrial fibrillation (AF) and eventually myocardial fibrosis, irrespective of ejection fraction (EF). Surgical correction (mitral valve repair) of MR removes the volume overload, hence unmasks pre-operative LV structure and function disturbances, including reduced EF and global longitudinal and circumferential strain, as well as LA volume and strain. This review aims at describing LA remodeling before and after surgical repair.

The Impact of Mental Stress on Cardiovascular Health-Part II.

Endothelial dysfunction is one of the earliest manifestations of atherosclerosis, contributing to its development and progression. Mental stress induces endothelial dysfunction through increased activity of the sympathetic nervous system, release of corticotropin-releasing hormone from the hypothalamus, inhibition of nitric oxide (NO) synthesis by cortisol, and increased levels of pro-inflammatory cytokines. Mental-stress-induced increased output of the sympathetic nervous system and concomitant withdrawal of the parasympathetic inflammatory reflex results in systemic inflammation and activation of a neural-hematopoietic-arterial axis. This includes the brainstem and subcortical regions network, bone marrow activation, release of leukocytes into the circulation and their migration to the arterial wall and atherosclerotic plaques. Low-grade, sterile inflammation is involved in all steps of atherogenesis, from coronary plaque formation to destabilisation and rupture. Increased sympathetic tone may cause arterial smooth-muscle-cell proliferation, resulting in vascular hypertrophy, thus contributing to the development of hypertension. Emotional events also cause instability of cardiac repolarisation due to brain lateralised imbalance of cardiac autonomic nervous stimulation, which may lead to asymmetric repolarisation and arrhythmia. Acute emotional stress can also provoke severe catecholamine release, leading to direct myocyte injury due to calcium overload, known as myocytolysis, coronary microvascular vasoconstriction, and an increase in left ventricular afterload. These changes can trigger a heart failure syndrome mimicking acute myocardial infarction, characterised by transient left ventricular dysfunction and apical ballooning, known as stress (Takotsubo) cardiomyopathy. Women are more prone than men to develop mental-stress-induced myocardial ischemia (MSIMI), probably reflecting gender differences in brain activation patterns during mental stress. Although guidelines on CV prevention recognise psychosocial factors as risk modifiers to improve risk prediction and decision making, the evidence that their assessment and treatment will prevent CAD needs further evaluation.