Prevalence, risk factors and potential implications of nail biting in adults with congenital heart disease.

BACKGROUND: Nail biting is a habit with potential health implications. Patients with congenital heart disease (CHD) are at increased risk of infections, with endocarditis being a particularly significant concern. Our aim was to establish the magnitude of this modifiable potential risk factor, namely nail biting, in a contemporary cohort of adult with CHD (ACHD). METHODS: Our prospective study included consecutive, unselected ACHD patients, categorised on nail-biting habits, analysing background demographics, health records, and behavioural factors. RESULTS: Of the 310 patients enrolled, 101 (33 %) were found to be current nail biters. Univariate logistic analysis revealed that younger age (OR: 1.30/10 years, p = 0.002), male gender (OR: 1.73, p = 0.029), greater CHD complexity (OR: 2.15, p = 0.002) and learning disability (OR: 3.51, p = 0.031) were associated with a significantly higher risk of nail biting. Multivariable analysis confirmed that younger age (OR: 1.29, p = 0.010), greater CHD complexity (OR: 1.89, p = 0.016), obesity (OR: 1.75, p = 0.038) and learning disability (OR: 3,87, p = 0.030) were significant predictors for nail biting. CONCLUSION: A third of ACHD patients attending a tertiary centre engage in nail biting, which may have detrimental effects. Such behaviour was more prevalent among younger, obese, complex CHD patients and those with learning disability. Lifestyle education and/or modifications warrant further improvement in this growing patient population.

Echocardiographic left atrial stiffness index predicts high left ventricular filling pressures in patients with acute heart failure: an observational study.

BACKGROUND: In acute heart failure (AHF) patients, non-invasive estimation of left ventricular filling pressures (LVFPs) appears crucial to guide management. Although poorly investigated, left atrial (LA) mechanics play a pivotal role in this setting. This report sought to assess the correlation of echocardiographic LA stiffness index with invasive LVFPs and its diagnostic accuracy as compared to other parameters used in clinical practice. METHODS: In this observational, prospective study, 104 patients with suspected acute coronary syndrome and signs/symptoms of AHF were enrolled. Available invasive estimation of LVFPs was required. Comprehensive echocardiography was performed for all patients, including LA reservoir strain (LARS). LA stiffness index was derived by speckle-tracking analysis and Tissue Doppler imaging as early diastolic transmitral inflow velocity/mitral annulus early diastolic velocity [E/e']/LARS. RESULTS: Invasively measured LVFPs showed a strong correlation with LA stiffness index (Spearman ρ = 0.773, p < 0.0001), as well as with LARS and E/e'. Receiver operating characteristic (ROC) curve analysis was used to demonstrate better accuracy performed by LA stiffness index than average E/e', LA volume or LARS alone, in predicting high LVFPs. Guideline-recommended assessment of diastolic function was finally compared to LARS and LA stiffness index performances in an independent population group; we were hence able to obtain a LA stiffness threshold of 0.48 with a positive predictive value of 91.7% and a negative predictive value of 88.9% in identifying patients with high LVFPs. CONCLUSIONS: For the first time, diagnostic performance of LA stiffness index has been investigated in a heterogeneous AHF population, providing correlations with invasively measured LVFPs and comparisons with established diastolic function metrics.

Precision Medicine in Acute Coronary Syndromes.

Nowadays, current guidelines on acute coronary syndrome (ACS) provide recommendations mainly based on the clinical presentation. However, greater attention is being directed to the specific pathophysiology underlying ACS, considering that plaque destabilization and rupture leading to luminal thrombotic obstruction is not the only pathway involved, albeit the most recognized. In this review, we discuss how intracoronary imaging and biomarkers allow the identification of specific ACS endotypes, leading to the recognition of different prognostic implications, tailored management strategies, and new potential therapeutic targets. Furthermore, different strategies can be applied on a personalized basis regarding antithrombotic therapy, non-culprit lesion revascularization, and microvascular obstruction (MVO). With respect to myocardial infarction with non-obstructive coronary arteries (MINOCA), we will present a precision medicine approach, suggested by current guidelines as the mainstay of the diagnostic process and with relevant therapeutic implications. Moreover, we aim at illustrating the clinical implications of targeted strategies for ACS secondary prevention, which may lower residual risk in selected patients.

Pulmonary congestion assessed by lung ultrasound in patients with severe aortic stenosis undergoing transcatheter aortic valve implantation: Prevalence and prognostic implications.

AIMS: Lung ultrasound (LUS) is a sensitive tool to assess pulmonary congestion (PC). Few data are available on LUS-PC evaluation in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve implantation (TAVI). The aim of this study was to assess the prevalence and prognostic impact of LUS-PC in patients with severe AS before and after TAVI. METHODS AND RESULTS: We designed a single-centre prospective study in patients referred for TAVI for severe AS (ClinicalTrials.gov identification number: NCT05024942). All patients underwent echocardiography and LUS (according to a simplified 8-zone scanning protocol) the day before and within 72 h after the procedure. The primary endpoint was the composite of all-cause mortality, hospitalization for heart failure and urgent medical visits for worsening dyspnoea at 12-month follow-up. A total of 127 patients were enrolled (mean age 81.1 ± 5.8 years; 54.3% female). Pre-TAVI LUS-PC was documented in 65 patients (51%). After TAVI, the prevalence of LUS-PC significantly decreased as compared to pre-TAVI evaluation, being documented in only 28 patients (22% vs. 51%, p < 0.001) with a median B-lines score of 4 (interquartile range [IQR] 0-11) versus 11 (IQR 6-19) pre-TAVI (p < 0.001). During a median follow-up of 12 (12-17) months, 25 patients (19.6%) met the composite endpoint. On multivariable Cox regression analysis, pre-TAVI LUS-PC was independently associated with cardiovascular events (hazard ratio 2.764, 95% confidence interval 1.114-6.857; p = 0.028). CONCLUSIONS: Lung ultrasonography reveals a high prevalence of PC in patients with severe AS undergoing TAVI, which is significantly reduced by the procedure. Pre-TAVI PC, measured by LUS, is an independent predictor of 1-year clinical outcome.

A multimodal approach to predict prosthesis-patient mismatch in patients undergoing valve-in-valve trans-catheter aortic valve implantation.

AIMS: The valve-in-valve transcatheter-aortic-valve-implantation (VIV-TAVI) represents an emerging procedure for the treatment of degenerated aortic bio-prostheses, and the occurrence of patient-prosthesis mismatch (PPM) after VIV-TAVI might affect its clinical efficacy. This study aimed to test a multimodal imaging approach to predict PPM risk during the TAVI planning phase and assess its clinical predictivity in VIV-TAVI procedures. METHODS: Consecutive patients undergoing VIV-TAVI procedures at our Institution over 6 years were screened and those treated by self-expandable supra-annular valves were selected. The effective orifice area (EOA) was calculated with a hybrid Gorlin equation combining echocardiographic data with invasive hemodynamic assessment. Severe PPM was defined according to such original multimodality assessment as EOAi≤0.65 cm2/m2 (if BMI < 30 kg/m2) or < 0.55 cm2/m2 (if BMI ≥ 30 kg/m2). The primary endpoint was a composite of all-cause mortality and valve-related re-hospitalization during the clinical follow-up. RESULTS: A total of 40 VIV-TAVI was included in the analysis. According to the pre-specified multimodal imaging modality assessment, 18 patients (45.0 %) had severe PPM. Among all baseline clinical and anatomical characteristics, estimated glomerular filtration rate before VIV-TAVI (OR 0.872, 95%CI[0.765-0.994],p = 0.040), the echocardiographic pre-procedural ≥moderate AR (OR 0.023, 95%CI[0.001-0.964],p = 0.048), the MSCT-derived effective internal area (OR 0.958, 95%CI[0.919-0.999],p = 0.046) and the implantation depth (OR 2.050, 95%CI[1.028-4.086],p = 0.041) resulted as independent predictors of severe PPM at multivariable logistic analysis. At a mean follow-up of 630 days, patients with severe PPM showed a higher incidence of the primary endpoint (9.1%vs.44.4 %;p = 0.023). CONCLUSION: In VIV-TAVI using self-expandable supra-annular valves, a multimodal imaging approach might improve clinical outcome predicting severe PPM occurrence.

An update on the mechanisms of Takotsubo syndrome: "At the end an acute coronary syndrome".

Takotsubo syndrome (TTS) is an acute reversible form of myocardial dysfunction, often preceded by a physical or emotional stressful event, that acts as a trigger. Despite, recent advances in the comprehension of the mechanisms leading to TTS, its pathophysiology is far from being completely understood. However, several studies seem to suggest that an acute coronary microvascular dysfunction may represent a crucial pathogenic mechanism involved in TTS occurrence. In this article, we aim to review the complex pathophysiology of TTS and the possible different mechanisms underlying this clinical condition, focusing on the role of coronary microvascular dysfunction and the remaining knowledge's gaps in the field.

Vaccines and Myocardial Injury in Patients Hospitalized for COVID-19 Infection: the CardioCOVID-Gemelli Study.

BACKGROUND: Myocardial injury is prevalent among patients hospitalized for COVID-19. However, the role of COVID-19 vaccines in modifying the risk of myocardial injury is unknown. OBJECTIVES: To assess the role of vaccines in modifying the risk of myocardial injury in COVID-19. METHODS: We enrolled COVID-19 patients admitted from March 2021 to February 2022 with known vaccination status and ≥1 assessment of hs-cTnI within 30 days from the admission. The primary endpoint was the occurrence of myocardial injury (hs-cTnI levels >99th percentile upper reference limit). RESULTS: 1019 patients were included (mean age 67.7±14.8 years, 60.8% male, 34.5% vaccinated against COVID-19). Myocardial injury occurred in 145 (14.2%) patients. At multivariate logistic regression analysis, advanced age, chronic kidney disease and hypertension, but not vaccination status, were independent predictors of myocardial injury. In the analysis according to age tertiles distribution, myocardial injury occurred more frequently in the III tertile (≥76 years) compared to other tertiles (I tertile:≤60 years;II tertile:61-75 years) (p<0.001). Moreover, in the III tertile, vaccination was protective against myocardial injury (OR 0.57, CI 95% 0.34-0.94; p=0.03), while a previous history of coronary artery disease was an independent positive predictor. In contrast, in the I tertile, chronic kidney disease (OR 6.94, 95% CI 1.31-36.79, p=0.02) and vaccination (OR 4.44, 95% CI 1.28-15.34, p=0.02) were independent positive predictors of myocardial injury. CONCLUSIONS: In patients ≥76 years, COVID-19 vaccines were protective for the occurrence of myocardial injury, while in patients ≤60 years, myocardial injury was associated with previous COVID-19 vaccination. Further studies are warranted to clarify the underlying mechanisms.

Left atrial structural and functional remodelling in Fabry disease and cardiac amyloidosis: A comparative analysis.

BACKGROUND: Fabry disease (FD) and transthyretin cardiac amyloidosis (TTR CA) are cardiomyopathies with hypertrophic phenotype that share several features, including left atrial (LA) enlargement and dysfunction, but direct comparative data are lacking. Aim of the present study was to perform a comparative analysis of LA remodelling between the two diseases. METHODS AND RESULTS: In this prospective study, a total of 114 patients (31 FD and 83 TTR CA) were included; all of them had left ventricular hypertrophy (LVH), defined as left ventricular (LV) wall thickness ≥ 12 mm. Despite similar degree of LVH, patients with TTR CA showed worse LV systolic and diastolic function. LA maximal volume index was not significantly different between the two groups (p = 0.084), while patients with TTR CA showed larger LA minimal volume index (p = 0.001). Moreover, all phases of LA mechanics were more impaired in the TTR CA group vs FD (reservoir: 6.9[4.2-15.5] vs 19.0[15.5-29.5], p < 0.001). After excluding patients with atrial fibrillation (AF), these differences remained clearly significant. In multivariable regression analyses, LA reservoir strain showed an independent correlation with TTR CA, controlling for demographic characteristics, AF and LV systolic and diastolic performance (p ≤ 0.001), whereas LV global longitudinal strain did not. Finally, among echocardiographic parameters, LA function demonstrated the highest accuracy in discriminating the two diseases. CONCLUSIONS: TTR CA is characterized by a more advanced LA structural and functional remodelling in comparison to patients with FD and similar degree of LVH. The association between TTR CA and LA dysfunction remains consistent after adjustment for potential confounders.

Clinical staging of Anderson-Fabry cardiomyopathy: An operative proposal.

As a slowly progressive form of hypertrophic cardiomyopathy (HCM), Anderson-Fabry disease (FD) resembles the phenotype of the most common sarcomeric forms, although significant differences in presentation and long-term progression may help determine the correct diagnosis. A variety of electrocardiographic and imaging features of FD cardiomyopathy have been described at different times in the course of the disease, and considerable discrepancies remain regarding the assessment of disease severity by individual physicians. Therefore, we here propose a practical staging of FD cardiomyopathy, in hopes it may represent the standard for cardiac evaluation and facilitate communication between specialized FD centres and primary care physicians. We identified 4 main stages of FD cardiomyopathy of increasing severity, based on available evidence from clinical and imaging studies: non-hypertrophic, hypertrophic - pre-fibrotic, hypertrophic - fibrotic, and overt dysfunction. Each stage is described and discussed in detail, following the principle that speaking a common language is critical when managing such complex patients in a multi-disciplinary and sometimes multi-centre setting.

Mechanisms, prevalence and management of cardiac arrhythmias in cancer patients: a comprehensive review.

Recently, prognosis and survival of cancer patients has improved due to progression and refinement of cancer therapies; however, cardiovascular sequelae in this population augmented and now represent the second cause of death in oncological patients. Initially, the main issue was represented by heart failure and coronary artery disease, but a growing body of evidence has now shed light on the increased arrhythmic risk of this population, atrial fibrillation being the most frequently encountered. Awareness of arrhythmic complications of cancer and its treatments may help oncologists and cardiologists to develop targeted approaches for the management of arrhythmias in this population. In this review, we provide an updated overview of the mechanisms triggering cardiac arrhythmias in cancer patients, their prevalence and management.

Prognostic Implications of the Extent of Cardiac Damage in Patients With Fabry Disease.

BACKGROUND: There is limited evidence on the risk stratification of cardiovascular outcomes in patients with Fabry disease (FD). OBJECTIVES: This study sought to classify FD patients into disease stages, based on the extent of the cardiac damage evaluated by echocardiography, and to assess their prognostic impact in a multicenter cohort. METHODS: Patients with FD from 5 Italian referral centers were categorized into 4 stages: stage 0, no cardiac involvement; stage 1, left ventricular (LV) hypertrophy (LV maximal wall thickness >12 mm); stage 2, left atrium (LA) enlargement (LA volume index >34 mL/m2); stage 3, ventricular impairment (LV ejection fraction <50% or E/e' ≥15 or TAPSE <17 mm). The study endpoint was the composite of all-cause death, hospitalization for heart failure, new-onset atrial fibrillation, major bradyarrhythmias or tachyarrhythmias, and ischemic stroke. RESULTS: A total of 314 patients were included. Among them, 174 (56%) were classified as stage 0, 41 (13%) as stage 1, 57 (18%) as stage 2 and 42 (13%) as stage 3. A progressive increase in the composite event rate at 8 years was observed with worsening stages of cardiac damage (log-rank P < 0.001). On multivariable Cox regression analysis, the staging was independently associated with the risk of cardiovascular events (HR: 2.086 per 1-stage increase; 95% CI: 1.487-2.927; P < 0.001). Notably, cardiac staging demonstrated a stronger and additive prognostic value, as compared with the degree of LV hypertrophy. CONCLUSIONS: In FD patients, a novel staging classification of cardiac damage, evaluated by echocardiography, is strongly associated with cardiovascular outcomes and may be helpful to refine risk stratification.

Early improvement of strain imaging parameters predicts long-term response to sacubitril/valsartan in patients with heart failure with reduced ejection fraction: An observational prospective study.

BACKGROUND: Management of patients affected by heart failure with reduced ejection fraction (HFrEF) has deeply changed thanks to novel pharmacological therapies, such as Sacubitril/Valsartan, which assured morbidity and mortality advantages in this population. These effects may be mediated by both left atrial (LA) and ventricular reverse remodeling, although left ventricular ejection fraction (LVEF) recovery still represents the main parameter of treatment response. METHODS: In this prospective, observational study, 66 patients with HFrEF and naïve from Sacubitril/Valsartan were enrolled. All patients were evaluated at baseline, at 3 months and 12 months from therapy initiation. Echocardiographic parameters, including speckle tracking analysis, LA functional and structural metrics, were collected at three timepoints. The endpoints of our study were: (1) to evaluate the effects of Sacubitril/Valsartan on echo measurements; (2) to assess the predictive role of early modifications of these parameters (expressed as ∆ 3-0 months) on long-term LVEF significant recovery, defined as >15% improvement from baseline. RESULTS: The majority of echocardiographic parameters evaluated progressively improved during the observation period, including LVEF, ventricular volumes and LA metrics. ∆(3-0 months) of LV Global Longitudinal Strain (LVGLS) and LA Reservoir Strain (LARS) were associated with significant LVEF improvement at 12 months (p < 0.001 and p = 0.019 respectively). A cut-off of ∆(3-0 months) LVGLS of 3% and of ∆(3-0 months) LARS of 2% could predict LVEF recovery with satisfactory sensitivity and specificity. CONCLUSIONS: LV and LA strain analysis may identify patients who adequately respond to HFrEF medical treatment and should be routinely used in the evaluation of these patients.

Inflammation across the spectrum of hypertrophic cardiac phenotypes.

The hypertrophic cardiomyopathy phenotype encompasses a heterogeneous spectrum of genetic and acquired diseases characterized by the presence of left ventricular hypertrophy in the absence of abnormal cardiac loading conditions. This "umbrella diagnosis" includes the "classic" hypertrophic cardiomyopathy (HCM), due to sarcomere protein gene mutations, and its phenocopies caused by intra- or extracellular deposits, such as Fabry disease (FD) and cardiac amyloidosis (CA). All these conditions share a wide phenotypic variability which results from the combination of genetic and environmental factors and whose pathogenic mediators are poorly understood so far. Accumulating evidence suggests that inflammation plays a critical role in a broad spectrum of cardiovascular conditions, including cardiomyopathies. Indeed, inflammation can trigger molecular pathways which contribute to cardiomyocyte hypertrophy and dysfunction, extracellular matrix accumulation, and microvascular dysfunction. Growing evidence suggests that systemic inflammation is a possible key pathophysiologic process potentially involved in the pathogenesis of cardiac disease progression, influencing the severity of the phenotype and clinical outcome, including heart failure. In this review, we summarize current knowledge regarding the prevalence, clinical significance, and potential therapeutic implications of inflammation in HCM and two of its most important phenocopies, FD and CA.

Left atrial strain analysis improves left ventricular filling pressures non-invasive estimation in the acute phase of Takotsubo syndrome.

AIMS: The aim of our study is to assess the ability of left atrial (LA) strain values to improve left ventricular and diastolic pressure (LVEDP) non-invasive estimation as compared with traditional echocardiographic indexes in the acute phase of Takotsubo syndrome (TTS) and to predict adverse in-hospital outcomes in this population. METHODS AND RESULTS: Consecutive TTS patients were prospectively enrolled. Left ventricular and diastolic pressure was measured at the time of catheterization. Transthoracic echocardiography was performed within 48 h from hospital admission. In-hospital complications (acute heart failure, death from any cause, and life-threatening arrhythmias) were collected. A total of 62 patients were analysed (72.2 ± 10.1 years, female 80%) and in-hospital complications occurred in 25 (40.3%). Left ventricular and diastolic pressure mean value was 24.53 ± 7.92 mmHg. Left atrial reservoir and pump strain values presented higher correlation with LVEDP (r -0.859, P < 0.001 and r -0.848, P < 0.001, respectively) in comparison with E/e ' ratio, left atrial volume index (LAVi), and tricuspid regurgitation (TR) peak velocity. In addition, at receiver-operating characteristic curve analysis, LA reservoir and pump strain resulted to be better predictors of LVEDP above the mean of our population [0.909 (95% CI 0.818-0.999, P < 0.001) and 0.889 (95% CI 0.789-0.988, P < 0.001)], respectively] as compared with E/e' ratio, LAVi, and TR peak velocity.Finally, LA reservoir strain resulted to be an independent predictor of worse in-hospital outcomes, together with LVEDP and left ventricular ejection fraction (all P < 0.001). CONCLUSION: In our study, lower LA reservoir and pump strain values were better predictors of LVEDP as compared with traditional echocardiographic indexes in the acute phase of TTS syndrome. Moreover, LA reservoir strain was an independent predictor of adverse in-hospital outcomes.

Clinical scenarios of hypertrophic cardiomyopathy-related mortality: Relevance of age and stage of disease at presentation.

The evolving epidemiology of hypertrophic cardiomyopathy (HCM) has progressively changed our perception of HCM-related mortality. However, recent studies detailing individual causes of death based on age and clinical setting are lacking. Thus, the present study aimed to describe the modes of death in a consecutive cohort of HCM patients based on presenting clinical features and stage of disease. METHODS: By retrospective analysis of a large HCM cohort, we identified 161 patients with >1 year follow-up who died between 2000 and 2020 and thoroughly investigated their modes of death. HCM stage at presentation was defined as "classic", "adverse remodeling" or "overt dysfunction". RESULTS: Of the 161 patients, 103 (64%) died of HCM-related causes, whereas 58 (36%) died of non-HCM-related causes. Patients who died of HCM-related causes were younger than those who died of non-HCM related causes. The most common cause of death was heart failure (HF). Sudden cardiac death (SCD) ranked third, after non cardiovascular death, and mostly occurred in young individuals. The proportion of HF related death and SCD per stage of disease was 14% and 27% in "classic", 38% and 21% in "adverse remodeling" and 74% and 10% in "overt dysfunction". CONCLUSIONS: Most HCM patients die due to complications of their own disease, mainly in the context of HF. While SCD tends to be juvenile, HF related deaths often occur in age groups no longer amenable to cardiac transplant. Modes of death vary with the stage of disease, with SCD becoming less prevalent in more advanced phases, when competitive risk of HF becomes overwhelming.

Cardiac Imaging in Childhood Cancer Survivors: A State-of-the-Art Review.

Childhood cancer survival has improved significantly in the past few decades, reaching rates of 80% or more at 5 years. However, with improved survival, early- and late-occurring complications of chemotherapy and radiotherapy exposure are becoming progressively more evident. Cardiovascular diseases represent the leading cause of non-oncological morbidity and mortality in this highly vulnerable population. Therefore, the necessity of reliable, noninvasive screening tools able to early identify cardiac complications early is now pre-eminent in order to implement prevention strategies and mitigate disease progression. Echocardiography, may allow identification of myocardial dysfunction, pericardial complications, and valvular heart diseases. However, additional imaging modalities may be necessary in selected cases. This manuscript provides an in-depth review of noninvasive imaging parameters studied in childhood cancer survivors. Furthermore, we will illustrate brief surveillance recommendations according to available evidence and future perspectives in this expanding field.