Totally percutaneous valve replacement for severe aortic regurgitation in a degenerating bioprosthesis

Recently, the feasibility and safety of percutaneous aortic valve replacement (PAVR) has been reported in the treatment of degenerative aortic valve stenosis in patients at high-risk for surgical aortic valve replacement (AVR).1 However, so far this therapy has been limited to patients with severe stenosis of the native valve. We report the case of a patient with severe aortic regurgitation owing to bioprosthesis dysfunction who was successfully treated by implantation of a CoreValve (CoreValve Inc, Irvine. Calif) prosthesis with a totally percutaneous approach

Twelve Variants Polygenic Score for Low-Density Lipoprotein Cholesterol Distribution in a Large Cohort of Patients With Clinically Diagnosed Familial Hypercholesterolemia With or Without Causative Mutations

: Background A significant proportion of individuals clinically diagnosed with familial hypercholesterolemia (FH), but without any disease-causing mutation, are likely to have polygenic hypercholesterolemia. We evaluated the distribution of a polygenic risk score, consisting of 12 low-density lipoprotein cholesterol (LDL-C)-raising variants (polygenic LDL-C risk score), in subjects with a clinical diagnosis of FH. Methods and Results Within the Lipid Transport Disorders Italian Genetic Network (LIPIGEN) study, 875 patients who were FH-mutation positive (women, 54.75%; mean age, 42.47±15.00 years) and 644 patients who were FH-mutation negative (women, 54.21%; mean age, 49.73±13.54 years) were evaluated. Patients who were FH-mutation negative had lower mean levels of pretreatment LDL-C than patients who were FH-mutation positive (217.14±55.49 versus 270.52±68.59 mg/dL, P<0.0001). The mean value (±SD) of the polygenic LDL-C risk score was 1.00 (±0.18) in patients who were FH-mutation negative and 0.94 (±0.20) in patients who were FH-mutation positive (P<0.0001). In the receiver operating characteristic analysis, the area under the curve for recognizing subjects characterized by polygenic hypercholesterolemia was 0.59 (95% CI, 0.56-0.62), with sensitivity and specificity being 78% and 36%, respectively, at 0.905 as a cutoff value. Higher mean polygenic LDL-C risk score levels were observed among patients who were FH-mutation negative having pretreatment LDL-C levels in the range of 150 to 350 mg/dL (150-249 mg/dL: 1.01 versus 0.91, P<0.0001; 250-349 mg/dL: 1.02 versus 0.95, P=0.0001). A positive correlation between polygenic LDL-C risk score and pretreatment LDL-C levels was observed among patients with FH independently of the presence of causative mutations. Conclusions This analysis confirms the role of polymorphisms in modulating LDL-C levels, even in patients with genetically confirmed FH. More data are needed to support the use of the polygenic score in routine clinical practice

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and ResultsAn lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score &gt;= 1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score &gt;= 1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level &gt;= 190 mg/dL (or from 68% to 50%, considering a more conservative formula). ConclusionsOur study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Lipoprotein(a) Genotype Influences the Clinical Diagnosis of Familial Hypercholesterolemia

: Background Evidence suggests that LPA risk genotypes are a possible contributor to the clinical diagnosis of familial hypercholesterolemia (FH). This study aimed at determining the prevalence of LPA risk variants in adult individuals with FH enrolled in the Italian LIPIGEN (Lipid Transport Disorders Italian Genetic Network) study, with (FH/M+) or without (FH/M-) a causative genetic variant. Methods and Results An lp(a) [lipoprotein(a)] genetic score was calculated by summing the number risk-increasing alleles inherited at rs3798220 and rs10455872 variants. Overall, in the 4.6% of 1695 patients with clinically diagnosed FH, the phenotype was not explained by a monogenic or polygenic cause but by genotype associated with high lp(a) levels. Among 765 subjects with FH/M- and 930 subjects with FH/M+, 133 (17.4%) and 95 (10.2%) were characterized by 1 copy of either rs10455872 or rs3798220 or 2 copies of either rs10455872 or rs3798220 (lp(a) score ≥1). Subjects with FH/M- also had lower mean levels of pretreatment low-density lipoprotein cholesterol than individuals with FH/M+ (t test for difference in means between FH/M- and FH/M+ groups &lt;0.0001); however, subjects with FH/M- and lp(a) score ≥1 had higher mean (SD) pretreatment low-density lipoprotein cholesterol levels (223.47 [50.40] mg/dL) compared with subjects with FH/M- and lp(a) score=0 (219.38 [54.54] mg/dL for), although not statistically significant. The adjustment of low-density lipoprotein cholesterol levels based on lp(a) concentration reduced from 68% to 42% the proportion of subjects with low-density lipoprotein cholesterol level ≥190 mg/dL (or from 68% to 50%, considering a more conservative formula). Conclusions Our study supports the importance of measuring lp(a) to perform the diagnosis of FH appropriately and to exclude that the observed phenotype is driven by elevated levels of lp(a) before performing the genetic test for FH

Progressive skin fibrosis is associated with a decline in lung function and worse survival in patients with diffuse cutaneous systemic sclerosis in the European Scleroderma Trials and Research (EUSTAR) cohort.

Objectives To determine whether progressive skin fibrosis is associated with visceral organ progression and mortality during follow-up in patients with diffuse cutaneous systemic sclerosis (dcSSc). Methods We evaluated patients from the European Scleroderma Trials and Research database with dcSSc, baseline modified Rodnan skin score (mRSS) ≥7, valid mRSS at 12±3 months after baseline and ≥1 annual follow-up visit. Progressive skin fibrosis was defined as an increase in mRSS &gt;5 and ≥25% from baseline to 12±3 months. Outcomes were pulmonary, cardiovascular and renal progression, and all-cause death. Associations between skin progression and outcomes were evaluated by Kaplan-Meier survival analysis and multivariable Cox regression. Results Of 1021 included patients, 78 (7.6%) had progressive skin fibrosis (skin progressors). Median follow-up was 3.4 years. Survival analyses indicated that skin progressors had a significantly higher probability of FVC decline ≥10% (53.6% vs 34.4%; p&lt;0.001) and all-cause death (15.4% vs 7.3%; p=0.003) than non-progressors. These significant associations were also found in subgroup analyses of patients with either low baseline mRSS (≤22/51) or short disease duration (≤15 months). In multivariable analyses, skin progression within 1 year was independently associated with FVC decline ≥10% (HR 1.79, 95% CI 1.20 to 2.65) and all-cause death (HR 2.58, 95% CI 1.31 to 5.09). Conclusions Progressive skin fibrosis within 1 year is associated with decline in lung function and worse survival in dcSSc during follow-up. These results confirm mRSS as a surrogate marker in dcSSc, which will be helpful for cohort enrichment in future trials and risk stratification in clinical practice

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P &lt; 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P &lt; 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P &lt; 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P &lt; 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P &lt; 0.001; OR(BP) = 2.4, P &lt; 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P &lt; 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P &lt; 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Prevalence, functional impact, and mortality of atrial fibrillation in an older Italian population (from the Pro.V.A. study).

The prevalence of atrial fibrillation (AF) is increasing in older patients faster than that of any other arrhythmia. AF is associated with increased morbidity and mortality. Data on AF in European populations are scarce. The aim of this study was to determine the prevalence and potential predictors of AF and to assess its impact on physical function and mortality in a representative sample of an Italian population >or=65 years of age. One thousand five hundred ninety-nine participants in the Pro.V.A. study, an observational cohort study of Italian subjects >or=65 years old, were assessed for health status, disability, and presence of AF at baseline and at a 4-year follow-up visit. After weighting, prevalence of AF at baseline was 7.4% and increased with advancing age. In subjects with AF, prevalences of stroke, coronary heart disease, peripheral artery disease, cognitive impairment, and physical disability were significantly higher (p or=65 years old, AF is strongly associated with heart failure, is an independent risk factor for mortality, and, in the presence of physical disability, could be considered a severity measurement of disability

Images in cardiovascular medicine. Right atrial mass in a patient with T-cell chronic lymphocytic leukemia: an unusual mechanism of thrombus formation.

A 71-year-old woman with refractory T-cell (CD4) chronic lymphocytic leukemia who had been treated with chemotherapy and leukapheresis with poor control of leucocytosis was admitted because of fever, cough, and chest pain. A chest x-ray showed a right basal pneumonia, and the cytological examination of sputum showed Aspergillus fumigatus (Figure 1). The ECG at admission showed a firstdegree atrioventricular block (Figure 2A). The patient was started on broad-spectrum antibiotics and liposomal amphotericin B. Shortly before admission, because of sinus tachycardia, an ECG with Holter monitoring was performed; it showed a run of supraventricular tachycardia (Figure 2B). Therefore, while in the hospital, the patient underwent cardiac evaluation. Two-dimensional echocardiography showed a round (2016 mm) floating mass in the right atrium, close to the superior caval vein (Figure 3A, Movie). A thrombus near the distal tip of the central venous catheter was suspected, and the patient was started on nadroparin 6000 U injected subcutaneously twice daily. At the time of echocardiography, blood counts showed severe leucocytosis (white blood cell count, 396.100/L; lymphocytes, 384.940/L). After 2 weeks of therapy with low-molecular-weight heparin, the patient underwent transesophageal echocardiography, which did not show any reduction of the atrial mass and excluded any relation to the central venous catheter (Figure 3B). A cardiac computed tomography scan was performed, which showed an 8-mm defect in the right atrium with irregular shape and contrast enhancement (Figure 3C). The patient died of multiorgan failure 52 days after admission. At autopsy, a multiorgan extensive leukemic infiltration was detected. The atrial mass, located at the junction of the inferior caval vein with the atrium and attached to the crista dividens, measured 201815 mm (figure 3D). Histologically, we found an infiltration of the atrial wall by clusters of cells that reached and disrupted the endocardial atrial surface, providing a likely cause for the stratified thrombotic apposition (Figure 4A through 4D). The clustered cells were CD45-positive (Figure 4C) and CD3-positive (Figure 4D) T-lymphocytes and were confined to the peduncle

Intensive cardiac care unit admission trends during the COVID-19 outbreak in Italy: a multi-center study

A significant decline in the admission to intensive cardiac care unit (ICCU) has been noted in Italy during the COVID-19 outbreak. Previous studies have provided data on clinical features and outcome of these patients, but information is still incomplete. In this multicenter study conducted in six ICCUs, we enrolled consecutive adult patients admitted to ICCU in three specific time intervals: from February 8 to March 9, 2020 [before national lockdown (pre-LD)], from March 10 to April 9, 2020 [during the first period of national lockdown (in-LD)] and from May 18 to June 17, 2020 [soon after the end of all containment measures (after-LD)]. Compared to pre-LD, in-LD was associated with a significant drop in the admission to ICCU for all causes (- 35%) and acute coronary syndrome (ACS; - 49%), with a rebound soon after-LD. The in-LD reduction was greater for women (- 49%) and NSTEMI (- 61%) compared to men (- 28%) and STEMI (- 33%). Length-of-stay, and in-hospital mortality did not show any significant change from to pre-LD to in-LD in the whole population as well as in the ACS group. This study confirms a notable reduction in the admissions to ICCUs from pre-LD to in-LD followed by an increment in the admission rates after-LD. These data strongly suggest that people, particularly women and patients with NSTEMI, are reluctant to seek medical care during lockdown, possibly due to the fear of viral infection. Such a phenomenon, however, was not associated with a rise in mortality among patients who get hospitalization