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Background Only one large series has been reported on fat embolism syndrome (FES), a condition caused by fat globules release into the circulation, primarily as consequence of bone fracture. Thus, more data on clinical features, therapies, and prognosis are needed. Methods and results The study screened 1090 manuscripts in PubMed and Web of Science on cases of FES published from June 2010 to June 2020. The authors identified 124 studies and included in the pooled-analysis 135 patients (>14 years), plus one additional unpublished case managed in Tongji hospital. All had confirmed diagnosis of FES with complete clinical data. The median age at presentation was 39 years, and 82 (61.8%) were men. FES was predominantly associated with bone fractures (78, 57.4%), particularly femur fracture (59, 43.4%). The most common clinical finding at the onset was respiratory abnormalities in 34.6% of all clinical presentations. Therapies included respiratory supportive care in 127 (93.4%) patients, application of corticosteroids in 22 (16.2%) and anticoagulant in 5 (3.7%) cases. Overall mortality was 30.2% (N = 41), and logistic regression analysis showed that corticosteroid therapy was significantly associated with reduced mortality with an OR of 0.143 (95%CI 0.029–0.711), while age ≥ 65 years and non-orthopedic conditions were significantly associated with increased mortality with an OR of 4.816 (95%CI 1.638–14.160) and 4.785 (95%CI 1.019–22.474). Conclusions FES has been associated with a larger mortality rate than previously observed, although publication bias can have led to overestimation of mortality. Finally, a potential protective effect of corticosteroid therapy has been suggested by the current analysis.

Acute myocarditis (AM), a recent-onset inflammation of the heart, has heterogeneous clinical presentations, varying from minor symptoms to high-risk cardiac conditions with severe heart failure, refractory arrhythmias, and cardiogenic shock. AM is moving from being a definitive diagnosis based on histological evidence of inflammatory infiltrates on cardiac tissue to a working diagnosis supported by high sensitivity troponin increase in association with specific cardiac magnetic resonance imaging (CMRI) findings. Though experts still diverge between those advocating for histological definition versus those supporting a mainly clinical definition of myocarditis, in the real-world practice the diagnosis of AM has undoubtedly shifted from being mainly biopsy-based to solely CMRI-based in most of clinical scenarios. It is thus important to clearly define selected settings where EMB is a must, as information derived from histology is essential for an optimal management. As in other medical conditions, a risk-based approach should be promoted in order to identify the most severe AM cases requiring appropriate bundles of care, including early recognition, transfer to tertiary centers, aggressive circulatory supports with inotropes and mechanical devices, histologic confirmation and eventual immunosuppressive therapy. Despite improvements in recognition and treatment of AM, including a broader use of promising mechanical circulatory supports, severe forms of AM are still burdened by dismal outcomes. This review is focused on recent clinical studies and registries that shed new insights on AM. Attention will be paid to contemporary outcomes and predictors of prognosis, the emerging entity of immune checkpoint inhibitors-associated myocarditis, updated CMRI diagnostic criteria, new data on the use of temporary mechanical circulatory supports in fulminant myocarditis. The role of viruses as etiologic agents will be reviewed and a brief update on pediatric AM is also provided. Finally, we summarize a risk-based approach to AM, based on available evidence and clinical experience.

Background Patients in heart transplantation (HTx) waiting list for advanced heart failure (HF) are susceptible to acute deterioration refractory to standard HF medical therapies. Limited data are available on long‐term in‐hospital continuous intravenous (IV) inotropic therapy as bridge to definite therapies. Methods and results We reviewed medical records of all heart transplant recipients treated in the pre‐HTx phase with in‐hospital continuous IV inotropes at our institution between 2012 and 2018. We analysed data before the beginning of continuous IV therapy and at the moment of HTx. We report data of 24 patients (mean age of 43.5 ± 15.7 years) treated with IV inotropes as bridge to HTx (median follow‐up of 28 months after HTx). The main length of IV inotropic therapy was 84 ± 66 days (min 22; max 264 days). At the beginning, the most frequently used inotrope was dopamine (median dosage of 3 mcg/kg/min, interquartile range 2.5–3.75), alone (n = 11, 46%) or in combination with other inotropes (n = 13, 54%). In 18 patients, the class of inotropes was changed during the hospitalization. We registered a progressive improvement of perfusion markers and neuro‐hormonal activation. Conclusion In‐hospital continuous parenteral inotropic therapy may serve as a temporary pharmacological bridge to HTx in patients with advanced HF that are actively listed to HTx with good reply in terms of prognosis and perfusion markers.

Fulminant myocarditis (FM) is a form of acute myocardial inflammation leading to rapid-onset hemodynamic instability due to cardiogenic shock or life-threatening arrhythmias. As highlighted by recent registries, FM is associated with high rates of death and heart transplantation, regardless of the underlying histology. Because of a paucity of evidence-based management strategies exists for this disease, an International workshop on FM was held in Wuhan, China, in October 2019, in order to share knowledge on the disease and identify areas of consensus. The present report highlights both agreements and controversies in FM management across the world, focusing the attention on areas of opportunity, FM definition, the use of endomyocardial biopsy and viral identification on heart specimens, treatment algorithms including immunosuppression and the timing of circulatory support escalation. This report incorporates the most recent recommendations from national and international professional societies. Main areas of interest and aims of future prospective observational registries and randomized controlled trials were finally identified and suggested.

Background Cardiac injury, as measured by troponin elevation, has been reported among hospitalized coronavirus disease 2019 (COVID-19) patients and portends a poor prognosis. However, how the dynamics of troponin elevation interplay with inflammation and coagulation biomarkers over time is unknown. We assessed longitudinal follow-up of cardiac injury, inflammation and coagulation markers in relation to disease severity and outcome. Methods We retrospectively assessed 2068 patients with laboratory-confirmed COVID-19 between January 29 and April 1, 2020 at Tongji Hospital in Wuhan, China. We defined cardiac injury as an increase in high sensitivity cardiac troponin-I (hs-cTnI) above the 99th of the upper reference limit. We explored the dynamics of elevation in hs-cTnI and the relationship with inflammation (interleukin [IL]-6, IL-8, IL-10, IL-2 receptor, tumor necrosis factor-α, C-reactive protein) and coagulation (d-dimer, fibrinogen, international normalized ratio) markers in non-critically ill versus critically ill patients longitudinally and further correlated these markers to survivors and non-survivors. Results Median age was 63 years (first to third quartile 51–70 years), 51.4% of whom were women. When compared to non-critically ill patients (N = 1592, 77.0%), critically ill (defined as requiring mechanical ventilation, in shock or multiorgan failure) patients (N = 476, 23.0%), had more frequent cardiac injury on admission (30.3% vs. 2.3%, p, Graphical abstract Unlabelled Image, Highlights • In COVID-19 patients increased levels of hs-cTnI beyond day 3 since admission portend a poor prognosis. • A consistent positive correlation of hs-cTnI with IL-6 and d-dimer could suggest nonspecific cytokine-mediated cardiotoxicity. • The risk for cardiac arrest and rhythm disturbances in patients with elevated hs-cTnI suggest an arrhythmogenic nature.

Objective We investigated the performance of four prognostic tools in predicting 180-day mortality for patients admitted for acute decompensated heart failure (ADHF) by calculating sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) over a range of risk thresholds, in addition to discrimination and calibration. Study Design and Setting We studied 1,458 patients. The risk assessment was performed using the Acute Decompensated Heart Failure National Registry (ADHERE) model and the Get With The Guidelines (GWTG), ADHF/NT-proBNP, and Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND) risk scores. Results C-statistics ranged from 0.727 for the ADHERE model to 0.767 for the ADHF/NT-proBNP score. The ADHF/NT-proBNP risk score, the ADHERE model, and the ASCEND risk score, but not the GWTG risk score, were also well calibrated. Sensitivity and PPV were modest at the >30% risk threshold and ranged from 55% for the ADHF/NT-proBNP risk score to 38.8% for the ADHERE model and from 46.7% for the ADHF/NT-proBNP risk score to 42.1% for the ASCEND risk score, respectively. There was a modest agreement between the risk scores in classifying the patients across risk strata or in classifying those who died as being at >30% risk of death. Conclusion Although risk assessment tools work well for stratifying patients, their use in estimating the risk of mortality for individuals has limited clinical utility.

We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular microaxial blood pumps. This case highlights a feasible approach for managing such patients who are not candidates for transplantation or durable ventricular assist devices. (Level of Difficulty: Intermediate.), Graphical abstract, We report a case of giant cell myocarditis in a 76-year-old patient managed with combined immunosuppression and biventricular intravascular m…

AIM To evaluate efficacy and safety of ATOMS implant in neurogenic patients with stress incontinence performing clean intermittent catheterization (CIC). METHODS We included all patients with neurogenic sacral/subsacral lesion and stress urinary incontinence, treated with ATOMS implant between January 2018 and March 2019. All patients received anamnesis, 24-hour pad test and pad count, physical examination, video urodynamic evaluation, Qualiveen questionnaire. All patients were followed up at 12 months after implantation. Patients were considered "continent" when dry or when wearing a security pad (social continence). RESULTS We treated eight male patients with a median age of 25 years, four affected by myelomeningocele, and four by cauda equine syndrome. The median preoperative 24-hour pad test was 225 g (interquartile range [IQR]: 180-275). During the surgical procedure, we did not fill the cushion to prevent postoperative urethral injuries when performing CIC in the early postoperative time. At a 12-month follow-up, we had a significant reduction in postoperative 24-hour pad test (median value: 7.5 g; IQR: 0-16.25; P

BACKGROUND The right ventriculoarterial coupling (R-V/A), a measure of right ventricular systolic dysfunction (RVSD) adaptation/maladaptation to chronic overload, and consequent pulmonary hypertension, has been little investigated in nonischemic dilated cardiomyopathy (NIDCM). We examined the correlates of R-V/A and traditional echocardiographic indices of RVSD, over the spectrum of pulmonary hypertension and tertiles of mean pulmonary artery pressures (PAPm). METHODS In 2016-2017, we studied 81 consecutive patients for heart transplant/advanced heart failure. Inclusion criteria were NIDCM, reduced ejection fraction (≤40%) and sinus rhythm. R-V/A was computed as the RV/pulmonary elastances ratio (R-Elv/P-Ea), derived from a combined right heart catheterization/transthoracic- echocardiographic assessment [right heart catheterization/transthoracic-echocardiographic (RHC/TTE)]. RESULTS A total of 68 patients (mean age 64 ± 7 years, 82% men) were eligible. After adjustments, R-Elv and P-Ea were higher in isolated postcapillary-pulmonary hypertension (Ipc-PH) than combined-pulmonary hypertension (Cpc-PH) (P = 0.004 and P = 0.002, respectively), whereas R-V/A progressively decreased over Ipc-PH and Cpc-PH (P = 0.006). According to PAPm increment, P-Ea congruently increased (P-Trend = 0.028), R-Elv progressively decreased (P-Trend

AIMS Male stress urinary incontinence (SUI) represents a complication after radical prostatectomy or benign prostatic obstruction surgery. The artificial urinary sphincter is considered the standard treatment but interest on minimally invasive devices, such as adjustable balloons, has recently increased. Aim of this study is to evaluate the efficacy and safety of the ProACT system. METHODS In this multicentric retrospective study, we reported the data from nine centers. Patients with SUI who underwent a ProACT device implantation for postoperative SUI and had a minimum follow-up of 24 months were included. Efficacy was evaluated at the maximum available follow-up and was assessed utilizing a 24-hour pad test. Patients were considered: "Dry" if presenting a urine leak weight lower than 8 g at the 24-hour pad test; "Improved" if presenting a reduction of urine leak higher than 50% (but >8 g/24 hours); "Failure" if presenting a reduction in urine leak lower than 50%. The evaluation included a record of intraoperative and long-term complications. RESULTS Safety and efficacy results are reported on 240 patients. 29.6% of patients were dry at 24 months, 37.5% were improved and 32.9% of patients were considered failures. The baseline mean pad weight of 367 g was reduced to 123 g at 24 months. Five-year follow-up on 152 patients showed similar efficacy. The complication rate was 22.5%, with the top complication being long-term balloon failure. CONCLUSIONS ProACT implantation represents a safe and efficacious treatment for male postoperative SUI at both medium and long-term follow up. 67.1% of patients were dry or improved at 24 months. The majority of complications are low grade.

BACKGROUND Fulminant myocarditis (FM) is a form of acute myocarditis characterized by severe left ventricular systolic dysfunction requiring inotropes and/or mechanical circulatory support. A single-center study found that a patient with FM had better outcomes than those with acute nonfulminant myocarditis (NFM) presenting with left ventricular systolic dysfunction, but otherwise hemodynamically stable. This was recently challenged, so disagreement still exists. OBJECTIVES This study sought to provide additional evidence on the outcome of FM and to ascertain whether patient stratification based on the main histologic subtypes can provide additional prognostic information. METHODS A total of 220 patients (median age 42 years, 46.3% female) with histologically proven acute myocarditis (onset of symptoms

AIMS Ageing and comorbidities are increasing frailty/complexity of heart failure (HF) patients globally. We assessed evolving trends over two decades according to patients' age and time of recruitment in a nationwide cardiology setting in Italy. METHODS AND RESULTS Chronic HF outpatients recruited between 1999 and 2018 (N = 14,823) were divided into 3 cohorts: 1999-2005 (N = 5404); 2006-2011 (N = 3971); 2012-2018 (N = 5448). We analyzed temporal changes in clinical characteristics, therapies, and outcome (1-year all-cause mortality/cardiovascular hospitalization), overall and by age group

Background The management of recurrent female stress urinary incontinence (SUI) still needs worldwide standardization. Few data on the role of urethral bulking agents (UBA) for the treatment of recurrent stress urinary incontinence exist. The aim of this study is to assess the efficacy and safety of urethral bulking agents for the treatment of recurrent SUI. Methods A multicenter, prospective study was conducted in four tertiary referral centers in two countries. All consecutive women with urodynamically proven recurrent SUI, and with a history of previous failed anti-incontinence surgical procedure (mid-urethral sling or single incision sling), treated by UBAs were included. We evaluated only patients who completed at least a 3yr follow up. Data regarding subjective outcomes (International Consultation on Incontinence Questionnaire-Short Form, Patient Global Impression of Improvement, Urogenital Distress Inventory score and patient satisfaction score), objective cure (stress test) rates, and adverse events were collected during follow-up. Univariable and multivariable analyses was performed to investigate outcomes. Results Forty-seven consecutive patients were enrolled. At 3-yr follow-up, all women were available for the evaluation. At 3 yr after surgery, 38 of 47 patients (81%) declared themselves cured. Similarly, at 3-yr evaluation, 39 of 47 patients (83%) were objectively cured. Only 5 patients (10.6 %) required reoperation for UBA failure. The urodynamic diagnosis of preoperative detrusor overactivity and the PDet Max filling phase ≥15 cmH2O (hazard ratio: 2.74; 95% CI, 1.64-10.7; p=0.009 and 1.62; 95% CI, 1.11-3.42; p=0.04, respectively) were the only predictors of failure. Only four complications were reported (8.5%). Conclusions The 3-yr results of this study showed that bulking agents is an appropriately effective and safe option for the treatment of recurrent SUI. The presence of preoperative concomitant detrusor overactivity is associated with a significant decrease of the efficacy of this procedure.

Background The outcomes of patients presenting with acute myocarditis and life-threatening ventricular tachyarrhythmias (LT-VA) are unclear. The aim of this study was to assess incidence and predictors of recurrence of major arrhythmic events (MAEs) after hospital discharge in such patients. Methods and results We retrospectively analysed 156 patients (median age 44 years; 77% males) discharged with a diagnosis of acute myocarditis and LT-VA from 16 hospitals worldwide. Diagnosis of myocarditis was based on histology or on the combination of increased markers of cardiac injury and cardiac magnetic resonance (CMR) Lake Louise criteria. MAEs were defined as the relapse, after discharge, of sudden cardiac death (SCD) or ventricular fibrillation defibrillated successfully or sustained ventricular tachycardia (sVT) requiring implantable cardioverter-defibrillator therapy or synchronized external cardioversion. Median follow-up period was 23 months (first to third quartile [Q1-Q3] 7-60). Fifty-eight (37.2%) patients experienced MAEs after discharge, at a median time of 8 months (Q1-Q3 2.5-24.0 months; 60.3% of MAEs within the first year). At multivariable Cox analysis, variables independently associated to MAEs were presentation with sVT (hazard ratio [HR] 2.90, 95% confidence interval [CI] 1.38-6.11); late gadolinium enhancement (LGE) involving ≥2 myocardial segments (HR 4.51, 95% CI 2.39-8.53); and absence of positive short-tau inversion recovery (STIR) (HR 2.59, 95% CI 1.40-4.79) at first CMR. Conclusions Among patients discharged with the diagnosis of myocarditis and LT-VA, 37.2% had recurrences of MAEs during follow-up. Initial CMR pattern and sVT at presentation stratify the risk of arrhythmic recurrence.

BACKGROUND: There is conflicting observational data on the survival benefit cardiac implantable electronic devices (CIED) in patients with LVADs. METHODS: Patients in whom an LVAD was implanted between January 2008 and April 2017 in the multinational Trans-Atlantic Registry on VAD and Transplant (TRAViATA) registry were separated into four groups based on the presence of CIED prior to LVAD implantation: none (n = 146), implantable cardiac defibrillator (ICD) (n = 239), cardiac resynchronization without defibrillator (CRT-P) (n = 28), and CRT with defibrillator (CRT-D) (n = 111). RESULTS: A total of 524 patients (age 52 years ±12, 84.4% male) were followed for 354 (interquartile range: 166-701) days. After multivariable adjustment, there were no differences in survival across the groups. In comparison to no device, only CRT-D was associated with late right ventricular failure (RVF) (hazard ratio 2.85, 95% confidence interval [CI] 1.42-5.72, p = 0.003). There was no difference in risk of early RVF across the groups or risk of ICD shocks between those with ICD and CRT-D. CONCLUSION: In a multinational registry of patients with LVADs, there were no differences in survival with respect to CIED subtype. However, patients with a pre-existing CRT-D had a higher likelihood of late RVF suggesting significant long-term morbidity in those with devices capable of LV‑lead pacing post LVAD implantation. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:340 pages:26-33 ispartof: location:Netherlands status: published

BACKGROUND: Geographic variations in management and outcomes of individuals supported by continuous-flow left ventricular assist devices (CF-LVAD) between the United States (US) and Europe (EU) is largely unknown. METHODS: We created a retrospective, multinational registry of 524 patients who received a CF-LVAD (either HVAD or Heartmate II) between January 2008 and April 2017. Follow up spanned from date of CF-LVAD implant to post-HTx period with a median follow up of 44.8 months. RESULTS: The cohort included 299 (57.1%) EU and 225 (42.9%) US patients. Although the US cohort was significantly older with a higher prevalence of comorbidities, survival was similar between the cohorts (US 63.1%, EU 68.4% at 5 years, unadjusted log-rank test p = 0.43).Multivariate analyses suggested that older age, higher body mass index, elevated creatinine, use of temporary mechanical circulatory support prior CF-LVAD, and implantation of HVAD were associated with increased mortality. Among CF-LVAD patients undergoing HTx, the median time on CF-LVAD support was shorter in the US, meanwhile US donors were younger. Finally, the pattern of adverse events (stroke, gastrointestinal bleedings, late right ventricular failure, and driveline infection) during support differed significantly between US and EU. CONCLUSIONS: Although waitlisted patients in the US on CF-LVAD have higher risk comorbid conditions, the overall outcome is similar in US and EU. Geographic variations with regards to donor characteristics, duration of CF-LVAD support prior to transplant, and adverse events on support can explain the disparity in the utilization of mechanical bridge to transplant strategy between US and EU. ispartof: INTERNATIONAL JOURNAL OF CARDIOLOGY vol:324 pages:122-130 ispartof: location:Netherlands status: published

Aims: The objective of the study was to analyze short-term outcomes and safety profile of the newly designed artificial urinary sphincters (AUSs) VICTO® and VICTOplus®. Methods: Data from the implant of VICTO® or VICTOplus® AUSs on a series of consecutive male patients with stress urinary incontinence (SUI) following radical prostatectomy (RP) were retrospectively collected in 3 tertiary referral centers between May 2017 and December 2019. Patients were affected by moderate-severe genuine SUI (200–400 or >400 g urine leakage in 24-h pad test) refractory to conservative treatment. Outcomes were evaluated through the 24-h pad test and the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form (ICIQ-UI-SF). Follow-up was scheduled after 3, 6, and 12 months and then when clinically needed. Nonparametric tests were applied in subgroup analyses. Results: Seventeen patients were enrolled: 8 were implanted with the VICTO® device and 9 with VICTOplus®. The median age at surgery was 69 (interquartile range (IQR) 60–75) years. The median follow-up was 15 (IQR 12–18) months. At 12 months, the dry rate was 76.4% and the social continence rate was 94%. The postoperative complication rate was 17.6%. All complications were classified as Clavien-Dindo I. No difference in terms of outcomes was observed between the VICTO® and the VICTOplus® subgroups. Conclusions: Preliminary outcomes of the VICTO® and VICTOplus® implantation are satisfactory. These devices may represent a safe and realistic solution for patients with moderate-severe SUI following RP.

Background There has been significant controversy about the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of patients with hypertension and coronavirus disease 2019. Methods and Results We retrospectively assessed 2297 hospitalized patients with coronavirus disease 2019 at Tongji Hospital in Wuhan, China, from January 10 to March 30, 2020; and identified 1182 patients with known hypertension on pre‐hospitalization therapy. We compared the baseline characteristics and in‐hospital mortality between patients with hypertension taking RAS inhibitors (n=355) versus non‐RAS inhibitors (n=827). Of the 1182 patients with hypertension (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group versus 95/827 (11.5%) patients in the non‐RAS inhibitors group ( P P P =0.007) and interleukin‐6 (median 6.0 versus 8.5 pg/mL; P =0.026) on admission. The protective effect of RAS inhibitors on mortality was confirmed in a meta‐analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29–0.65, P Conclusions In a large single center retrospective analysis, we observed a protective effect of pre‐hospitalization use of RAS inhibitors on mortality in patients with hypertension and coronavirus disease 2019, which might be associated with reduced inflammatory response.

Background Elderly >80 years represent the most rapidly expanding population segment in Europe. Chronic heart failure (CHF) affects over 10% of this group and generates a major M&M burden. We analyzed the temporal trends in characteristics, therapy and outcomes over two decades in octogenarians enrolled in our nationwide registry. Methods According to the recruitment epoch, among 14.283 CHF patients first enrolled in the registry since 1–1999 through 5–2018, we divided those aged 80+ (2520,17.6%) into 3 cohorts: 1999–2005 (547, 10%); 2006–2011 (659, 16.5%); 2012–2018 (1314, 14.1%). We analyzed trends over time in characteristics, therapy, 1-year all-cause mortality and proportion admitted to hospital. Results From 1999 to 2018 the proportion of 80+ CHF patients (60% men, 84±3 years, LVEF 41±1%, HFrEF 49%) rose from 10% to 24%. Across the 3 epochs (Table 1) we observed a shift towards the HFpEF phenotype with an increase in its driving factors (obesity, diabetes, hypertension, AFib). At the same time, the proportion treated with recommended therapies rose. Cumulative 1-year mortality did not differ across the 3 epochs (Fig.1 top), whereas the proportion of 80+ hospitalized overall, for CV causes and for decompensated HF, declined (Fig. 1 bottom). Conclusions During 20 years, the clinical characteristics of octogenarians enrolled in a nationwide CHF registry have deeply changed, reflecting demographic variations, the evolution of CV risk factors and improved management. There was a consistent implementation of BB, MRA and devices. Survival of 80+ remained stable, but the proportion of those hospitalized for CV causes, and specifically decompensated HF, declined. These data suggest that cardiologists' input may contribute to decrease the socioeconomic burden of CHF in the elderly. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Fondazione per il Tuo cuore – Heart Care Foundation (HCF) ONLUS

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases., Central Illustration, Highlights • The burden of CVD, in number of DALYs and deaths, continues to increase globally. • CVD burden attributable to modifiable risk factors continues to increase globally. • Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.

The diagnosis of bladder pain syndrome/interstitial cystitis (BPS/IC) is substantially clinical, according to the ESSIC definition. After clinical suspicion, it is mandatory to exclude confusable diseases and identify phenotypical aspects of the disease. There are different severity grades, involved organs, possible allergies, and impact on quality of life. Some of these aspects can vary in the natural history of disease as well as after treatment. To facilitate a diagnostic pathway and follow-up, we suggest a standardized system. We elaborated a chart with 12 items, each considering a peculiar aspect/domain of the disease: micturition diary, Visual Analogue Scale (VAS), presence of pelvic/systemic pain, symptom prevalence (pain/LUTS), validated questionnaires, associated pathologies, allergies and intolerances, ESSIC classification, bladder anatomical capacity, and pelvic floor involvement. The grid is proposed to be a simple and immediate instrument to characterize the clinical picture and follow the variations over time.

Coronavirus disease 2019 (COVID-19) pneumonia tends to affect cardiovascular system and cause cardiovascular damage. This study aimed to explore the prevalence of myocardial injury and risk factors for mortality in patients with COVID-19 pneumonia.Two hundred and twenty-four consecutive patients with confirmed diagnosis of SARS-CoV-2 infection and definite outcomes (discharge or death) were retrospectively analyzed. Laboratory results including myocardial biomarkers, oxygen saturation, inflammatory indicators and coagulation function were compared between survivors and non-survivors. Univariate and multivariate logistic regression model were used to explore risk factors for in-hospital mortality, and a chart with different combinations of risk factors was constructed to predict mortality.Two hundred and three patients were included in the final analysis, consisting of 145 patients who recovered and 58 patients who died. Compared with survivors, non-survivors were older, with more comorbidities, more severe inflammation and active coagulation function, higher levels of myocardial biomarkers and lower SaOOur results suggest that SARS-CoV-2 infection may induce myocardial injury and consequently exacerbate the clinical course and worsen prognosis. Abnormal d-dimer, CK-MB, Troponin I and CRP are risk factors for short-term mortality.

Cardiac and cerebrovascular diseases are currently the leading causes of mortality and disability worldwide. Both the heart and brain display similar vascular anatomy, with large conduit arteries running on the surface of the organ providing tissue perfusion through an intricate network of penetrating small vessels. Both organs rely on fine tuning of local blood flow to match metabolic demand. Blood flow regulation requires adequate functioning of the microcirculation in both organs, with loss of microvascular function, termed small vessel disease (SVD) underlying different potential clinical manifestations. SVD in the heart, known as coronary microvascular dysfunction, can cause chronic or acute myocardial ischemia and may lead to development of heart failure. In the brain, cerebral SVD can cause an acute stroke syndrome known as lacunar stroke or more subtle pathological alterations of the brain parenchyma, which may eventually lead to neurological deficits or cognitive decline in the long term. Coronary microcirculation cannot be visualized in vivo in humans, and functional information can be deduced by measuring the coronary flow reserve. The diagnosis of cerebral SVD is largely based on brain magnetic resonance imaging, with white matter hyperintensities, microbleeds, and brain atrophy reflecting key structural changes. There is evidence that such structural changes reflect underlying cerebral SVD. Here, we review interactions between SVD and cardiovascular risk factors, and we discuss the evidence linking cerebral SVD with large vessel atheroma, atrial fibrillation, heart failure, and heart valve disease.

Background: We explored the relation between blood concentrations of monocyte/lymphocyte subsets and carotid artery plaque macrophage content, measured by positron emission tomography (PET) with 11C-PK11195. Methods and results: In 9 patients with carotid plaques we performed 11C-PK11195-PET/computed tomography angiography imaging and measurement of absolute concentrations and frequencies of circulating monocytes and T-cell subsets. Plaque standardized uptake value (SUV) for 11C-PK11195 was negatively correlated with concentrations of total monocytes (r = −0.58, p = 0.05) and CD14++CD16−HLA-DR+ classical subset (r = −0.82, p = 0.005). These correlations hold true also in relation to plaque target to background ratio. No correlation was observed between plaque SUV and CD3+T lymphocytes, CD4+T lymphocytes nor with activated CD3+CD4+T cells expressing HLA-DR. Conclusions: We first demonstrated a reduction in the absolute concentration of monocytes and particularly in classical monocytes expressing HLA-DR in the presence of an increased uptake of 11C-PK11195 in carotid plaques. The present work, despite being a pilot study comprising only a small number of subjects provides new insights in the search for specific cellular biomarkers with potential diagnostic and prognostic value in patients with a known carotid plaque. Keywords: Carotid plaque, 11C-PK11195 uptake, Classical monocytes, Positron emission tomography, Atherosclerosis

Cardiomyopathies are diseases of the myocardium, often genetically determined, associated with heterogeneous phenotypes and clinical manifestations. Despite significant progress in the understanding of these conditions, available treatments mostly target late complications, whereas approaches that promise to interfere with the primary mechanisms and natural history are just beginning to surface. The last decade has witnessed the establishment of large international cardiomyopathy registries, paralleled by advances in cardiac imaging and genetic testing, deeper understanding of the pathophysiology and growing involvement by the pharmaceutical industry. As a result, the number of molecular interventions under scrutiny is increasing sharply.

Context Neuromodulation is considered in patients with non-neurogenic lower urinary tract dysfunction (LUTD) not responsive to conservative treatment. Objective To systematically review the available studies on efficacy and safety of sacral neuromodulation (SNM) and percutaneous tibial nerve stimulation (PTNS) in non-neurogenic LUTDs not responsive to conservative treatments. Evidence acquisition A literature research was conducted in PubMed/Medline and Scopus, restricted to articles in English, published between January 1998 and June 2017, with at least 20 patients and 6 mo of follow-up. Evidence synthesis Twenty-one reports were identified. Concerning SNM, the improvement of ≥50% in leakage episodes ranged widely between 29% and 76%. Overall dry rate ranged between 43% and 56%. Overall success/improvement rate in PTNS varied between 54% and 59%. Symptom improvement or efficacy in interstitial cystitis/bladder pain syndrome patients appeared to be lower compared with other indications in both techniques. Safety data showed fewer side effects in patients submitted to PTNS. Conclusions Neuromodulation gives good results and is a safe therapy for patients with overactive bladder or chronic nonobstructive urinary retention with long-lasting efficacy. Moreover, PTNS has been shown to have good success rates and fewer side effects compared with SNM. These data have to be confirmed with long-term follow-up. Patient summary Sacral neuromodulation can improve low urinary tract symptoms in selected patients; it appears to be a safe therapy for nonresponders to standard medical therapies. Percutaneous tibial nerve stimulation (PTNS) is a less invasive technique that gives good results in short time with fewer side effects. However, we must consider that PTNS has not been tested in the long term and results are lower if compared with SNM.

Background Eosinophilic myocarditis (EM) is an acute life-threatening inflammatory disease of the heart. Neither large case series nor clinical trials on this specific myocarditis have been reported. Objectives Based on a systematic revision of all published histologically proven cases, this study aimed to describe the clinical presentation, treatment, and outcome of EM. Methods The study screened 443 manuscripts in MEDLINE and EMBASE on cases of EM published until June 2017. The authors identified 264 patients and included in the main analysis 179 patients admitted to hospital with histologically proven EM. Results Median age was 41 years (interquartile range: 27 to 53 years) with similar prevalence in both sexes; pediatric cases (≤16 years of age) accounted for 10.1%. The main symptom at presentation was dyspnea (59.4%), with peripheral eosinophilia observed in 75.9%. Median left ventricular ejection fraction at presentation was 35% (interquartile range: 25% to 50%). The disorders most frequently associated with EM were hypersensitivity and eosinophilic granulomatosis with polyangiitis, which accounted for 34.1% and 12.8% of cases, respectively, whereas idiopathic or undefined forms accounted for 35.7% of cases. Steroids were administered in 77.7% of patients. A temporary mechanical circulatory support (n = 30) was instituted in 16.8% of patients. In-hospital death was 22.3% (n = 40), with the highest occurrence in the hypersensitivity form (36.1%; p = 0.026). Conclusions EM has a poor prognosis during the acute phase, despite a publication bias that could have led to an overestimation of mortality. Associated conditions are identified in approximately 65% of cases. Specific trials and multicenter registries are needed to provide evidence-based treatments to improve in-hospital outcome.

Background The presence of late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR) has diagnostic and prognostic value in patients with acute myocarditis (AM). Aim of our study was to quantify the changes in LGE extension (LGE%) early after AM and evaluate its relations with biventricular function and morphology. Methods We investigated 76 consecutive patients with AM (acute onset of chest pain/heart failure/ventricular arrhythmias not explained by other causes, and raised troponin) that met CMR criteria based on myocardial oedema at T2-weighted images and LGE on post-contrast images at median time of 6 days from onset of symptoms. We quantified LGE% at baseline and after 148 days in 49 patients. Results Median left ventricular (LV)-ejection fraction (EF) was 64% (interquartile range [Q1–Q3]: 56–67%), and LGE% 9.4% (Q1–Q3: 7.5–13.2%). LGE% was correlated with LV end-systolic volume index (LV-ESVi; r = + 0.34; p = 0.003). LGE% was inversely correlated with LV-EF (r = − 0.31; p = 0.009) and time to CMR scan (r = − 0.25; p = 0.028). In the 49 patients with a second CMR scan, despite no significant variations in LV-EF, a significant decrease of LGE% was observed (p < 0.0001) with a relative reduction of 42% compared with baseline. Patients showing increased LV-ESVi at follow up had a lower decrease of LGE% (p = 0.038). Conclusions In the acute phase of AM the LGE extension is a dynamic process that reflects impairment of LV function and is time dependent. LGE% appears one of the CMR parameters with the largest relative variations in the first months after AM

Supplemental Digital Content is available in the text., Myocarditis is an inflammatory disease of the heart that may occur because of infections, immune system activation, or exposure to drugs. The diagnosis of myocarditis has changed due to the introduction of cardiac magnetic resonance imaging. We present an expert consensus document aimed to summarize the common terminology related to myocarditis meanwhile highlighting some areas of controversies and uncertainties and the unmet clinical needs. In fact, controversies persist regarding mechanisms that determine the transition from the initial trigger to myocardial inflammation and from acute myocardial damage to chronic ventricular dysfunction. It is still uncertain which viruses (besides enteroviruses) cause direct tissue damage, act as triggers for immune-mediated damage, or both. Regarding terminology, myocarditis can be characterized according to etiology, phase, and severity of the disease, predominant symptoms, and pathological findings. Clinically, acute myocarditis (AM) implies a short time elapsed from the onset of symptoms and diagnosis (generally

A novel betacoronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly across the globe since December 2019. Coronavirus disease 2019 (COVID-19) has a significantly higher mortality rate than seasonal influenza and has disproportionately affected older adults, especially those with cardiovascular disease and related risk factors. Adverse cardiovascular sequelae, such as myocarditis, acute myocardial infarction, and heart failure, have been reported in patients with COVID-19. No established treatment is currently available; however, several therapies, including remdesivir, hydroxychloroquine and chloroquine, and interleukin (IL)-6 inhibitors, are being used off-label and evaluated in ongoing clinical trials. Considering these therapies are not familiar to cardiovascular clinicians managing these patients, this review describes the pharmacology of these therapies in the context of their use in patients with cardiovascular-related conditions.

Highlights • Age and fibrocalcific carotid plaques are associated with lower total brain volume. • Fibrocalcific carotid plaques are associated with lower gray matter volumes. • White matter volumes are associated with the extent of carotid atherosclerosis. • Grey and white matter likely have differential susceptibility to processes., Background and aims Extent of subclinical atherosclerosis has been associated with brain parenchymal loss in community-dwelling aged subjects. Identification of patient-related and plaque-related markers could identify subjects at higher risk of brain atrophy, independent of cerebrovascular accidents. Aim of the study was to investigate the relation between extent and characteristics of carotid plaques and brain atrophy in asymptomatic patients with no indication for revascularization. Methods and results Sixty-four patients (aged 69 ± 8 years, 45% females) with carotid stenosis

Coronavirus disease 2019 (COVID‐19) patients with cardiac injury have an increased risk of mortality. It remains to be determined the mechanism of cardiac injury and the identification of specific conditions that affect the heart during COVID‐19. We present the case of a 76‐year‐old woman with COVID‐19 pneumonia that developed a takotsubo syndrome (TTS). Although the patient presented normal left ventricular ejection fraction and normal levels of troponin on admission, after 16 days in intensive care unit due to respiratory distress, she suddenly developed cardiogenic shock. Shock occurred few hours after a spontaneous breathing trial through her tracheostomy. Bed‐side echocardiographic revealed apical ballooning promptly supporting the diagnosis of TTS. She was successfully treated with deep sedation and low dosage of epinephrine. The relevance of this case is that TTS can occur in the late phase of COVID‐19. Awareness of late TTS and bed‐side echocardiographic evaluation can lead to prompt identification and treatment.

Effective treatments for mutated transthyretin (TTR)-related cardiac amyloidosis are limited. Heart transplantation or combined liver-heart transplantation are the most successful options, although results rely on underline mechanism and systemic nature of the disease. In this report, we present the first case of a Caucasian patient with the p.Val122Ile mutated TTR-related cardiac amyloidosis treated with heart transplantation due to this gene mutation frequent in Afro-Americans with a prevalent isolated heart involvement. The choice of isolated heart transplantation instead of combined heart and liver transplantations was based on (1) severe and progressive cardiac disease, (2) evidence of a gene mutation generally associated with isolated cardiac disease and (3) absence of relevant extra-cardiac involvement (with the possible exception of mild peripheral neuropathy). In any case, the very short post-transplant observation period of 10 months does not allow any conclusions on the long-term course of the presented strategy. Finally, it is the first European Caucasian family with the p.Val122Ile TTR mutation that has been described. Till now, very few Caucasian cases of p.Val122Ile mutated TTR-related cardiac amyloidosis have been reported. The patient and some members of his family also had mild peripheral neuropathy suggesting a regional phenotypic heterogeneity of European Caucasian TTR p.Val122Ile.

ProACT is an extra urethral bulking system made of a silicone balloon connected with a dual lumen tubing (12–14 cm) to a titanium scrotal port that allows the postoperative adjustment (Fig. 6.1). It was introduced in the European market in 2000 as the first non-circumferential compressive device. The continence mechanism is guaranteed by a bilateral compression of the urethra, augmenting maximum urethral closure pressure (MUCP). In a study by Reuvers et al. this mechanism was demonstrated in a cohort of 23 successfully implanted patients in which a significant increase in MUCP from 58 cmH2O to 79 cmH2O was observed [1].

BACKGROUND The aim of this study was to evaluate efficacy and safety of the ATOMS system for the treatment of postoperative stress urinary incontinence (SUI). METHODS We included all consecutive male patients referring for postoperative SUI and treated with ATOMS system from June 2013 to July 2017. Patients received anamnesis, 24 h Pad Test, Pad count, physical examination, urodynamic evaluation, ICIQ-UI SF questionnaire. We excluded patients with low bladder capacity and compliance, uncontrolled detrusor overactivity. RESULTS We treated 98 patients with median age of 70.21±10.02 years. The most common cause of SUI was open radical prostatectomy in 79 patients. Ten patients had undergone urethrotomy, 7 bladder neck incision, 14 adjuvant radiotherapy. Thirty-nine patients suffered of mild incontinence (24 h Pad Test