Immune Checkpoint Inhibitors and Atherosclerotic Vascular Events in Cancer Patients.

In clinical trials and meta-analysis, atherosclerotic vascular events (AVEs) during treatment with immune-checkpoint inhibitors (ICIs) have been reported with low incidence. However, preclinical data suggest that these drugs can promote atherosclerosis inflammation and progression of atherosclerosis plaques, and there is now growing and convincing evidence from retrospective studies that ICIs increase the risk of atherosclerotic vascular events including arterial thrombosis, myocardial infarction and ischemic stroke. Prospective studies are needed to increase knowledge on long-term effect of ICIs or their combinations with other cardio-toxic drugs, but in the meantime a careful assessment and optimization of cardiovascular risk factors among patients treated with ICIs is advisable.

Increased aortic stiffness in adults with chronic indeterminate Chagas disease.

An ever-increasing number of patients with chronic indeterminate Chagas disease are diagnosed with early vascular and cardiac abnormalities, as cardiovascular imaging becomes more sensitive. However, the currently available information on aortic stiffness (a prognostic marker for adverse cardiovascular outcomes) in these patients is scarce. In this study, we consecutively recruited 21 asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease and 14 Bolivian adults, who were seronegative for Trypanosoma cruzi infection. No participants had a prior history of heart disease, hypertension, diabetes, chronic kidney disease or atrial fibrillation. Carotid-femoral pulse wave velocity (cf-PWV), carotid-radial PWV (cr-PWV), carotid intima-media thickness and conventional echocardiographic measurements were recorded in all participants. Patients with chronic indeterminate Chagas disease had significantly higher cf-PWV (7.9±1.3 vs. 6.4±1.1 m/s, p = 0.003) and greater HOMA-estimated insulin resistance than subjects without Chagas disease. The two groups did not significantly differ in terms of age, sex, smoking, adiposity measures, blood pressure, plasma lipids, fasting glucose levels as well as cr-PWV, carotid intima-media thickness measurements, left ventricular mass and function. Presence of chronic indeterminate Chagas disease was significantly associated with increasing cf-PWV values (ß coefficient: 1.31, 95% coefficient interval 0.44 to 2.18, p = 0.005), even after adjustment for age, sex, heart rate, systolic blood pressure and insulin resistance. In conclusion, asymptomatic Bolivian adult patients with chronic indeterminate Chagas disease have an early and marked increase in aortic stiffness, as measured by cf-PWV, when compared to Bolivian adults who were seronegative for Trypanosoma cruzi infection.

Nonalcoholic Fatty Liver Disease Is Associated With Higher 1-year All-Cause Rehospitalization Rates in Patients Admitted for Acute Heart Failure.

Repeat hospitalization due to acute heart failure (HF) is a global public health problem that markedly impacts on health resource use. Identifying novel predictors of rehospitalization would help physicians to determine the optimal postdischarge plan for preventing HF rehospitalization. Nonalcoholic fatty liver disease (NAFLD) is an emerging risk factor for many heart diseases, including HF. We assessed whether NAFLD at hospital admission predicts 1-year all-cause rehospitalization in patients with acute HF. We enrolled all patients consecutively admitted for acute HF to our General Medicine Division, from January 2013 to April 2014, after excluding patients with acute myocardial infarction, severe heart valve diseases, malignancy, known liver diseases, and those with volume overload related to extracardiac causes. NAFLD was diagnosed by ultrasonography and exclusion of competing etiologies. The primary outcome of the study was the 1-year all-cause rehospitalization rate. Among the 107 patients enrolled in the study, the cumulative rehospitalization rate was 12.1% at 1 month, 25.2% at 3 months, 29.9% at 6 months, and 38.3% at 1 year. Patients with NAFLD had markedly higher 1-year rehospitalization rates than those without NAFLD (58% vs 21% at 1 y; P < 0.001 by the log-rank test). Cox regression analysis revealed that NAFLD was associated with a 5.5-fold increased risk of rehospitalization (adjusted hazard ratio 5.56, 95% confidence interval 2.46-12.1, P < 0.001) after adjustment for multiple HF risk factors and potential confounders. In conclusion, NAFLD was independently associated with higher 1-year rehospitalization in patients hospitalized for acute HF.

Profile of Trypanosoma cruzi infection in a tropical medicine reference center, Northern Italy.

BACKGROUND: Chagas disease (CD) is endemic in Central and South America, Mexico and even in some areas of the United States. However, cases have been increasingly recorded also in non-endemic countries. The estimated number of infected people in Europe is in a wide range of 14000 to 181000 subjects, mostly resident in Spain, Italy and the United Kingdom. METHODOLOGY/PRINCIPAL FINDINGS: Retrospective, observational study describing the characteristics of patients with CD who attended the Centre for Tropical Diseases (Negrar, Verona, Italy) between 2005 and 2013. All the patients affected by CD underwent chest X-ray, ECG, echocardiography, barium X-ray of the oesophagus and colonic enema. They were classified in the indeterminate, cardiac, digestive or mixed category according to the results of the screening tests. Treatment with benznidazole (or nifurtimox in case of intolerance to the first line therapy) was offered to all patients, excluding the ones with advanced cardiomiopathy, pregnant and lactating women. Patients included were 332 (73.9% women). We classified 68.1% of patients as having Indeterminate Chagas, 11.1% Cardiac Chagas, 18.7% as Digestive Chagas and 2.1% as Mixed Form. Three hundred and twenty-one patients (96.7%) were treated with benznidazole, and most of them (83.2%) completed the treatment. At least one adverse effect was reported by 27.7% of patients, but they were mostly mild. Only a couple of patients received nifurtimox as second line treatment. CONCLUSIONS/SIGNIFICANCE: Our case series represents the largest cohort of T. cruzi infected patients diagnosed and treated in Italy. An improvement of the access to diagnosis and cure is still needed, considering that about 9200 infected people are estimated to live in Italy. In general, there is an urgent need of common guidelines to better classify and manage patients with CD in non-endemic countries.

Agreement between the new EuroSCORE II, the Logistic EuroSCORE and the Society of Thoracic Surgeons score: implications for transcatheter aortic valve implantation.

BACKGROUND: The Logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) and the Society of Thoracic Surgeons (STS) score are routinely used to identify patients at high surgical risk as potential candidates for transcatheter aortic valve implantation (TAVI). AIMS: To compare the new EuroSCORE II with the Logistic EuroSCORE and the STS score. METHODS: From October 2006 to June 2011, patients with severe symptomatic aortic stenosis who underwent a TAVI were enrolled prospectively. RESULTS: Among 272 patients, the EuroSCORE II was significantly lower and moderately correlated with the Logistic EuroSCORE (9±8% vs. 23±14%, P<0.01; r=0.61, P<0.001), but similar to and poorly correlated with the STS (10±9%, P=0.10; r=0.25, P<0.001). Based on recommended high-risk thresholds (Logistic EuroSCORE≥20%; STS≥10%), a EuroSCORE II≥7% provided the best diagnostic value. However, using the EuroSCORE II, Logistic EuroSCORE or STS score, only 51%, 58% and 37% of patients, respectively, reached these thresholds. Contingency analyses showed that agreements between the EuroSCORE II and the Logistic EuroSCORE or the STS score were modest or poor, respectively, with a risk assessment different in 28% and 36% of patients, respectively. CONCLUSIONS: A EuroSCORE II≥7% corresponded to a Logistic EuroSCORE≥20% or STS score≥10%, but correlations and agreements were at best modest and only approximately half of the patients reached these thresholds. Our results highlight the limits of current scoring systems and reinforce the European guidelines stressing the importance of clinical judgment in addition to risk scores.

Identification of high-risk chronic heart failure patients in clinical practice: role of changes in left ventricular function.

BACKGROUND: Left ventricular (LV) dysfunction and remodeling are key pathophysiological features underlying disease progression in chronic heart failure (CHF). HYPOTHESIS: To describe the course of LV dysfunction and identify predictors and prognostic impact of changes in LV volumes and function in stable CHF patients under optimal therapy. METHODS: There were 318 consecutive CHF outpatients who underwent a repeated echocardiographic evaluation at baseline and at 1 year and subsequently followed-up for at least 12 months. The end point of the study was all-cause mortality. RESULTS: Mean LV ejection fraction (LVEF) was 33 ± 7% at baseline and 36 ± 9% at follow-up. Twenty-four percent of patients had an improvement of LVEF >5 absolute points (group 1); 58% remained stable (group 2), 17% worsened at >5 absolute points (group 3). Age, New York Heart Association class, diuretic dose, renal function, and baseline LVEF were independent predictors of LVEF improvement at 1 year. At the Cox analysis, patients in group 3 had a 4-fold higher risk of death when compared with group 1 (hazard ratio: 3.99, 95% confidence interval: 1.6-9.9, P = 0.002), independently of age, etiology, and symptoms severity. CONCLUSIONS: In stable CHF outpatients, LV function improves in 24% of cases; a modest decrease in LV systolic function is associated with a significantly higher risk of all-cause mortality, independent of other markers of disease severity.

Determinants of regurgitant volume in mitral regurgitation: contrasting effect of similar effective regurgitant orifice area in functional and organic mitral regurgitation.

BACKGROUND: Quantitative assessment of the severity of mitral regurgitation (MR) is based on the calculation of the effective regurgitant orifice (ERO), a measure of lesion severity, and of the regurgitant volume (RVol), a measure of left ventricular volume overload. We aimed at evaluating the determinants of RVol in both organic (OMR) and functional mitral regurgitation (FMR). METHODS AND RESULTS: MR severity was quantitatively assessed using the proximal isovelocity surface area (PISA) method in 240 patients, 142 with OMR and 98 patients with FMR. By definition, ERO and RVol were strongly correlated both in patients with OMR and FMR (both R = 0.90, P < 0.0001) but the slopes of the regression lines were significantly different (P < 0.0001). This difference remained significant in patients with elevated systolic pulmonary artery pressure (SPAP > 40 mmHg, P < 0.0001) but not in patients with normal SPAP (≤40 mmHg, P = 0.09). In multivariate analysis, independent determinants of RVol were ERO (P < 0.0001), MR mechanism (FMR/OMR) (P = 0.0003) and SPAP (P = 0.03). In patients with elevated SPAP, ERO (P < 0.0001), left ventricular ejection fraction (LVEF) (P = 0.03), and MR mechanism (P = 0.03) were independently associated with RVol, whereas in patients with normal SPAP, ERO (P < 0.0001) was the only independent determinant of RVol. CONCLUSION: In the present study, we evaluated the contrasting effect of similar lesion severity in OMR and FMR and showed that similar ERO were associated with lower RVol in FMR compared with OMR. The regurgitant volume is the result of complex interactions of anatomic lesions, LVEF, and SPAP and our results highlight the importance of taking into account these parameters when interpreting RVol values in clinical practice, especially in FMR.

Progression of Left Ventricular Dysfunction and Remodelling under Optimal Medical Therapy in CHF Patients: Role of Individual Genetic Background.

Background. Neurohormonal systems play an important role in chronic heart failure (CHF). Due to interindividual heterogeneity in the benefits of therapy, it may be hypothesized that polymorphisms of neurohormonal systems may affect left ventricular (LV) remodelling and systolic function. We aimed to assess whether genetic background of maximally treated CHF patients predicts variations in LV systolic function and volumes. Methods and Results. We prospectively studied 131 CHF outpatients on optimal treatment for at least six months. Echocardiographic evaluations were performed at baseline and after 12 months. Genotype analysis for ACE I/D, ß1adrenergic receptor (AR) Arg389Gly, ß2AR Arg16Gly, and ß2AR Gln27Glu polymorphisms was performed. No differences in baseline characteristics were detected among subgroups. ACE II was a significant predictor of improvement of LV end-diastolic and end-systolic volume (P = .003 and P = .002, respectively) but not of LV ejection fraction (LVEF); ß1AR389 GlyGly was related to improvement of LVEF (P = .02) and LV end-systolic volume (P = .01). The predictive value of polymorphisms remained after adjustment for other clinically significant predictors (P < .05 for all). Conclusions. ACE I/D and ß1AR Arg389Gly polymorphisms are independent predictors of reverse remodeling and systolic function recovery in CHF patients under optimal treatment.