Atherosclerosis and the Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside-Part 1.

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis, while atherosclerosis, with its inflammatory microenvironment, can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review, we aim to summarize the state of the art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology and exert a positive impact on precision cardiology and cardio-oncology.

Cardiovascular Effects of Immune Checkpoint Inhibitors: More Than Just Myocarditis.

PURPOSE OF REVIEW: Immune checkpoint inhibitors have reshaped the treatment of cancer, but they are characterized by peculiar toxicity consisting of immune-related adverse events that may potentially affect any organ or system. In this review, we summarize data on clinical presentation, diagnosis, pathogenesis, and management of the main immune-related cardiovascular toxicities of immune checkpoint inhibitors. RECENT FINDINGS: The most relevant immune-related cardiovascular toxicity is myocarditis, but other non-negligible reported events include non-inflammatory heart failure, conduction abnormalities, pericardial disease, and vasculitis. More recently, growing evidence suggests a role for immune checkpoint inhibitors in accelerating atherosclerosis and promoting plaque inflammation, thus leading to myocardial infarction. Immune checkpoint inhibitors are associated with several forms of cardiovascular toxicity; thus, an accurate cardiovascular baseline evaluation and periodical monitoring are required. Furthermore, the optimization of cardiovascular risk factors before, during, and after treatment may contribute to mitigating both short-term and long-term cardiovascular toxicity of these drugs.

ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO).

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.

Cardiovascular Risk After Adjuvant Trastuzumab in Early Breast Cancer: An Italian Population-Based Cohort Study.

BACKGROUND: Although trastuzumab (T) represents the standard of care for the adjuvant treatment of HER2-positive early-stage breast cancer, contrasting results are available about the cardiac toxicity associated to its use. We conducted a multiregional population-based cohort investigation aimed to assess both the short- and long-term cardiovascular (CV) outcomes in women with early breast cancer treated with T-based or standard adjuvant chemotherapy (CT). MATERIALS AND METHODS: We used health care use databases of six Italian regions, overall accounting for 42% of the Italian population. The study cohort was made by all women surgically treated for breast cancer who started a first-line adjuvant T-based or CT treatment. Patients treated with T were 1:2 matched to those treated with CT based on date of treatment start, age, and presence of CV risk factors. Short- and long-term CV outcomes (heart failure and cardiomyopathy) were measured, respectively, after 1 year and at the end of follow-up. RESULTS: Among 28,599 women who met the inclusion criteria, 6,208 T users were matched to 12,416 CT users. After a mean follow-up of 5.88 years, short- and long-term cumulative CV risk were 0.8% and 2.6% in patients treated with T and 0.2% and 2.8% in those treated with CT, respectively. Adjusted hazard ratios were 4.6 (95% confidence interval [CI], 2.6-8.0) for short-term and 1.2 (95% CI, 0.9-1.6) for long-term CV risk. DISCUSSION: In our large real-world investigation, T-associated cardiotoxicity was limited to the treatment period. The addition of T to adjuvant CT did not result in long-term worsening of CV events. IMPLICATIONS FOR PRACTICE: Adjuvant trastuzumab-based chemotherapy represents the backbone therapy in patients with HER2-positive early breast cancer. Although well tolerated, cardiovascular events can manifest during or after therapy because of treatment-related toxicities. In this wide multicenter and unselected cohort, long-term symptomatic cardiotoxicity was low and limited to the treatment period. The findings suggest that developing tools that would be adequately able to predict cardiac toxicity at an early stage remains an important area in which additional research efforts are needed.

Cardio-oncology: the new frontier of clinical and preventive cardiology.

Even if cancer and cardiovascular diseases are considered two distinct diseases, an intricate interconnection between these conditions has been established. Increased risk of malignancy has been identified in patients with cardiovascular disease, as well as a greater propensity to the development of cardiovascular diseases has been observed in patients with cancer. The development of cardiotoxicity following exposure to certain anticancer drugs only partially explains this relationship. Shared risk factors and common pathogenic mechanisms suggest the existence of a common biology and a complex interplay between these two conditions. Due to improving longevity and therapeutic advances, the number of patients affected or potentially at risk of developing these two diseases is constantly increasing and currently, several drugs against cancer from anthracyclines to checkpoint inhibitors, can also cause a wide range of unexpected cardiovascular side effects. Management of these issues in clinical practice is an emerging challenge for cardiologists and oncologists, and led to the development of a new dedicated discipline called cardio-oncology. Surveillance and prevention strategies as well as interventions to reduce cardiovascular risk and prevent cardiotoxicities are the primary objectives of cardio-oncology. In this review, we explore the etiopathogenesis common to cardiovascular disease and cancer and the complex interplay between them. We also report the main characteristics of the drugs responsible for cardiotoxicity, highlighting the available strategies for optimal patient management based on a multidisciplinary approach in the cardio-oncology setting.

Are aortic coarctation and rheumatoid arthritis different models of aortic stiffness? Data from an echocardiographic study.

BACKGROUND: Patients who underwent a successful repair of the aortic coarctation (CoA) show high risk for cardiovascular (CV) events. Mechanical and structural abnormalities in the ascending aorta (Ao) might have a role in the prognosis of CoA patients. We analyzed the elastic properties of Ao measured as aortic stiffness index (AoSI) in CoA patients in the long-term period and we compared AoSI with a cohort of 38 patients with rheumatoid arthritis (RA) and 38 non-RA matched controls. METHODS: Data from 19 CoA patients were analyzed 28 ± 13 years after surgery. Abnormally high AoSI was diagnosed if AoSI > 6.07% (95th percentile of the AoSI detected in our reference healthy population). AoSI was assessed at the level of the aortic root by two-dimensional guided M-mode evaluation. RESULTS: CoA patients showed more than two-fold higher AoSI compared to RA and controls (9.8 ± 12.6 vs 4.8 ± 2.5% and 3.1 ± 2.0%, respectively; all p < 0.05 and in 5 of 19 patients with CoA (26%) AoSI was exceptionally high. The 5 patients with abnormally high AoSI were older with higher BP, LV mass and prevalence of LV diastolic dysfunction. Multiple linear regression analysis revealed that AoSI was independently related to the presence of LV hypertrophy and higher LV relative wall thickness. CONCLUSIONS: CoA patients have higher AoSI levels than RA patients and non-RA matched controls. AoSI levels are abnormally high in a small sub-group of CoA patients who show a very high-risk clinical profile for adverse CV events.

Progression of Renal Impairment and Chronic Kidney Disease in Chronic Heart Failure: An Analysis From GISSI-HF.

BACKGROUND: Data on the natural change in renal function in patients with chronic heart failure (HF) are limited. METHODS AND RESULTS: Estimated glomerular filtration rate (eGFR) was assessed over 36 months in 6934 patients included in the GISSI-HF study. Associations from baseline, changes in renal function, and occurrence of cardiovascular death or HF hospitalization were assessed. Mean age was 67 years, mainly men (78%), and mean eGFR was 68 mL • min-1 • 1.73 m-2. Change in eGFR in the 1st year was -1.5 ± 16 mL • min-1 • 1.73 m-2, and over 36 months it was -3.7 ± 18 mL • min-1 • 1.73 m-2. Over the latter period, only 25% deteriorated ≥1 Kidney Disease Outcomes Quality Initiatives (KDOQI) class of chronic kidney disease (CKD). Fifteen percent of patients had >15 mL • min-1 • 1.73 m-2 decrease in eGFR in the 1st 12 months. Lower eGFR was associated with outcome: hazard ratio (HR) 1.10, 95% confidence interval (CI) 1.08-1.10 (P < .001) per 10 mL • min-1 • 1.73 m-2 decrease, as well as every 10 mL • min-1 • 1.73 m-2 decrease over the 1st year (HR 1.10, 95% CI 1.04-1.17; P < .001). A deterioration in eGFR >15 mL • min-1 • 1.73 m-2 in the 1st year showed the highest risk of events (HR 1.22, 95% CI 1.10-1.36; P < .001). CONCLUSIONS: Mean decrease in renal function over time in patients with chronic HF was modest. Only 25% deteriorated ≥1 KDOQI class of CKD after 3 years. Any decrease in eGFR over time was associated with strongly increased event rates.

ANMCO/AIOM/AICO Consensus Document on clinical and management pathways of cardio-oncology: executive summary.

Cardiovascular disease and cancer are leading causes of death. Both diseases share the same risk factors and, having the highest incidence and prevalence in the elderly, they often coexist in the same individual. Furthermore, the enhanced survival of cancer patients registered in the last decades and linked to early diagnosis and improvement of care, not infrequently exposes them to the appearance of ominous cardiovascular complications due to the deleterious effects of cancer treatment on the heart and circulatory system. The above considerations have led to the development of a new branch of clinical cardiology based on the principles of multidisciplinary collaboration between cardiologists and oncologists: Cardio-oncology, which aims to find solutions to the prevention, monitoring, diagnosis and treatment of heart damage induced by cancer care in order to pursue, in the individual patient, the best possible care for cancer while minimizing the risk of cardiac toxicity. In this consensus document we provide practical recommendations on how to assess, monitor, treat and supervise the candidate or patient treated with potentially cardiotoxic cancer therapy in order to treat cancer and protect the heart at all stages of the oncological disease. Cardiovascular diseases and cancer often share the same risk factors and can coexist in the same individual. Such possibility is amplified by the deleterious effects of cancer treatment on the heart. The above considerations have led to the development of a new branch of clinical cardiology, based on multidisciplinary collaboration between cardiologist and oncologist: the cardio-oncology. It aims to prevent, monitor, and treat heart damages induced by cancer therapies in order to achieve the most effective cancer treatment, while minimizing the risk of cardiac toxicity. In this paper, we provide practical recommendations on how to assess, monitor, treat and supervise patients treated with potential cardiotoxic cancer therapies.

Value of Combined Circumferential and Longitudinal Left Ventricular Systolic Dysfunction to Predict Adverse Outcome in Patients with Asymptomatic Aortic Stenosis.

BACKGROUND AND AIM OF THE STUDY: Patients with asymptomatic aortic stenosis (AS) may have left ventricular systolic dysfunction (LVSD) defined as an impairment of the circumferential and/or longitudinal (C&L) myocardial fibers, despite a preserved left ventricular ejection fraction (LVEF). An assessment was made as to whether the combined LVSD of C&L fibers has a prognostic impact in asymptomatic AS. METHODS: A total of 200 asymptomatic AS patients was analyzed. Midwall shortening and mitral annular peak systolic velocity were considered as indices of C&L function and classified as low if <16.5% and <8.5 cm/s, respectively. The primary outcome was a composite of major cardiovascular events (MACE), including aortic valve-related and ischemic cardiovascular-related events. RESULTS: During a 25-month follow up period, MACE occurred in 69 patients (35%),while 46 of 72 patients (64%) had C&L LVSD and 23 of 128 patients (18%) had not (p <0.001). Cox analysis identified C&L LVSD as an independent MACE predictor, together with aortic transvalvular peak gradient, E/E' ratio and excessive left ventricular mass. C&L-LVSD also predicted the occurrence of aortic valve-related events and ischemic cardiovascular-related events analyzed separately. A receiver operating characteristic curve analysis showed that the area under the curve (AUC) for C&L LVSD in predicting MACE was 0.77, significantly higher (p = 0.002, z-statistic) than the AUCs of C&L fibers considered individually (0.64 and 0.63, respectively). CONCLUSION: C&L-LVSD provides additional prognostic information into traditional risk factors for patients with asymptomatic AS.

Echocardiographic markers of inducible myocardial ischemia at baseline evaluation preparatory to exercise stress echocardiography.

BACKGROUND: Tissue Doppler Imaging (TDI) is a sensible and feasible method to detect longitudinal left ventricular (LV) systolic dysfunction (LVSD) in patients with diabetes mellitus, hypertension or ischemic heart disease. In this study, we hypothesized that longitudinal LVSD assessed by TDI predicted inducible myocardial ischemia independently of other echocardiographic variables (assessed as coexisting potential markers) in patients at increased cardiovascular (CV) risk. METHODS: Two hundred one patients at high CV risk defined according to the ESC Guidelines 2012 underwent exercise stress echocardiography (ExSEcho) for primary prevention. Echocardiographic parameters were measured at rest and peak exercise. RESULTS: ExSEcho classified 168 (83.6 %) patients as non-ischemic and 33 (16,4 %) as ischemic. Baseline clinical characteristics were similar between the groups, but ischemic had higher blood pressure, received more frequently beta-blockers and antiplatelet agents than non-ischemic patients. The former had greater LV size, lower relative wall thickness and higher left atrial systolic force (LASF) than the latter. LV systolic longitudinal function (measure as peak S') was significantly lower in ischemic than non-ischemic patients (8.7 ± 2.1 vs 9.7 ± 2.7 cm/sec, p = 0.001). The factors independently related to myocardial ischemia at multivariate logistic analysis were: lower peak S', higher LV circumferential end-systolic stress and LASF. CONCLUSIONS: In asymptomatic patients at increased risk for adverse CV events baseline longitudinal LVSD together with higher LV circumferential end-systolic stress and LASF were the factors associated with myocardial ischemia induced by ExSEcho. The assessment of these factors at standard echocardiography might help the physicians for improving the risk stratification among these patients for ExSEcho.

Does treatment assignment influence the prognosis of patients with symptomatic severe aortic stenosis?

OBJECTIVE: Aortic valve replacement (AVR) is the standard therapy in patients with symptomatic aortic stenosis (AS). In high surgical risk patients, alternative therapeutic options to medical treatment (MT) such as trans-catheter aortic valve implantation (TAVI) or balloon aortic valvuloplasty (BAV) have been proposed. In this study we evaluated whether treatment assignment influences per se the prognosis of these subjects. PATIENTS AND METHODS: Criteria for treatment assignment were based on patient's clinical conditions, Logistic EuroSCORE and other co-morbidities ignored by EuroSCORE. Due to baseline clinical differences between patients with diverse treatment assignment, we used propensity score matching to achieve balance. RESULTS: 368 patients were studied: 141 underwent AVR, 127 TAVI, 49 BAV and 51 MT. 84 events (deaths for all causes) occurred during 14 months of follow-up: 11 AVR (8%), 26 TAVI (20%), 18 MT (35%), 29 BAV group (59%). Traditional Cox analysis identified treatment assignment as independent predictor of events (HR 1.82 [CI 1.10-3.25]) together with lower left ventricular ejection fraction, impaired renal function and history of heart failure. Matched Cox analysis by propensity score confirmed treatment assignment as an independent prognosticator of events (HR 1.90 [CI 1.27-2.85]), and showed similar rate events in TAVI and AVR patients, while it was significantly increased in BAV and MT patients. CONCLUSIONS: Treatment assignment may influence outcome of symptomatic patients with AS.

Analysis of left atrial performance in patients with type 2 diabetes mellitus without overt cardiac disease and inducible ischemia: high prevalence of increased systolic force related to enhanced left ventricular systolic longitudinal function.

OBJECTIVES: In patients with chronic pressure overload, higher left atrial systolic force (LASF) is associated with high-risk cardiovascular (CV) phenotype, with increased left ventricular (LV) mass, concentric hypertrophy, and diastolic dysfunction. In hypertension and aortic stenosis, LASF predicts increased rate of CV events independent of traditional risk factors. Moreover, LASF is an independent predictor of heart failure in diabetic and nondiabetic patients. Limited data are available about LASF and its relationship with LV systolic function in type 2 diabetes mellitus (T2DM). METHODS: We used baseline clinic and echocardiographic data from 333 patients recruited in the SHORTWAVE study evaluating LV and left atrial performance in T2DM patients without cardiac disease. LASF was calculated by Manning's method and defined high when exceeded 16 Kdynes (90th percentile of LASF found in 120 healthy subjects used as controls). RESULTS: Mean LASF was 15.8 Â ± 9.4 Kdynes/cm(2) and showed a close positive correlation with peak mitral annular systolic velocity (function of LV longitudinal fibers), independent of E/E', age, systolic blood pressure, heart rate, and concentric geometry (multiple R = 0.57, P < 0.0001). Such independent correlation (tested in patients with and without concomitant hypertension) was confirmed at multiple logistic regression analysis where patients were dichotomized for having high (119 = 36%) or normal LASF. CONCLUSIONS: High LASF is present in one third of T2DM patients without overt cardiac disease and is positively and independently related to an increased LV longitudinal shortening function, suggesting a close interaction between LV systolic and diastolic function.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with asymptomatic aortic stenosis.

BACKGROUND: Early detection of left ventricular (LV) systolic dysfunction is pivotal in the management of patients with aortic stenosis (AS). LV circumferential and/or longitudinal shortening may be impaired in these patients despite LV ejection fraction is preserved. We focused on prevalence and factors associated with combined impairment of circumferential and longitudinal shortening (C&L) in asymptomatic AS patients. METHODS: Echocardiographic and clinical data from 200 patients with asymptomatic AS of any degree without history of heart failure and normal LV ejection fraction were analyzed. C&L were evaluated by mid-wall shortening (MS) and tissue Doppler mitral annular peak systolic velocity (S'), and classified low if <16.5% and if <8.5 cm/sec, respectively (10th percentiles of controls). RESULTS: Combined C&L dysfunction was detected in 72 patients (36%). The variables associated with this condition were higher LV mass (OR 1.02 [CI 1.01-1.04], P = 0.03), concentric LV geometry (OR 4.30 [CI 1.79-10.34], P = 0.001), increasing pulmonary artery wedge pressure (by E/e' ratio; OR 1.11 [CI 1.04-1.19], P = 0.001). The relation of MS and peak S' was linear and slightly significant in the whole population (r = 0.23; F statistic=0.001), absent in patients with C&L dysfunction (r = 0.04; F = ns), negative (linear model) in the subgroup of patients without C&L dysfunction (r = -0.22; F = 0.02). CONCLUSIONS: C&L dysfunction is present in more than one-third of patients with asymptomatic AS and is associated with concentric LV geometry and higher degree of diastolic dysfunction. The relation between MS and peak S' largely varies in the subgroups with different C&L function.

Left atrial work in patients with stable chronic heart failure: factors associated and prognostic role.

BACKGROUND: Limited information is available on left atrial (LA) work in chronic heart failure (CHF) patients. We evaluated correlates and prognostic role of LA work in 243 CHF patients using as reference for normal LA work values 230 healthy controls. METHODS: Left atrial work was assessed by computation of LA kinetic energy (LAKE) from the formula: 0.5 × m × A(2) where m is LA stroke volume × blood density, and A is transmitral Doppler peak atrial velocity. The prespecified primary endpoint of the study was major cardiovascular (CV) events, a composite endpoint defined as CV death + hospitalization for heart failure (HF). RESULTS: Left atrial kinetic energy was 3.9 ± 2.7 in CHF patients and 2.6 ± 1.4 Kdynes/m(2) in controls (P < 0.001). Abnormally high LAKE (>5.4 Kdynes/m(2) = mean + 2 SD of the controls) was found in 19% of CHF patients and 4% of controls (P < 0.001). LAKE was independently associated with an increased shortening of left ventricular (LV) longitudinal fibers and renal dysfunction. CV death or hospitalization for decompensated HF occurred in 66% and 20% of patients with abnormally high and normal LAKE, respectively (P < 0.001). Abnormally high LAKE, not LA size, was an independent predictor of events hazard ratio (HR) 3.92 [95% CI 1.96-7.84] together with renal dysfunction and lower LV ejection fraction. CONCLUSION: In CHF patients, LAKE is significantly higher than in healthy controls, the prevalence of abnormally high LAKE is near fivefold higher in the former than in the latter. LAKE depends on systolic LV and renal function and is a strong predictor of CV death and hospitalization for HF. LA work has an incremental prognostic value over LA size.

Left ventricular systolic dysfunction in chronic kidney disease: from asymptomatic changes in geometry and function to overt heart failure.

A bidirectional relationship between kidney and heart function is present in all stages of cardiac and renal disease, from the asymptomatic phase of left ventricular systolic dysfunction to overt heart failure, as well as from the initial reduction of glomerular filtration rate to end-stage kidney disease, respectively. The simultaneous presence of both diseases has a significant impact on prognosis and requires specific therapeutic strategies. The early recognition of abnormalities of renal and myocardial function may have a relevant influence on management of combination of these conditions.

[Diffuse large B-cell lymphoma with heart involvement: the relevance of the multidisciplinary and multiparameter approach]. / Linfoma diffuso a grandi cellule B con coinvolgimento cardiaco: l'importanza dell'approccio multidisciplinare e multiparametrico.

Lymphoma patients are at high risk of cardiovascular events due to anthracycline cardiotoxicity and, in rare cases, related to heart infiltration. The presence of cardiac masses adds further complexity to the management of lymphoma patients beyond myocardial chemotherapy-related toxicity, given possible unpredictable acute complications such as arrhythmias, atrioventricular block, myocardial ischemia, pericardial effusion and cardiac tamponade. Here we describe the clinical presentation and successful multidisciplinary management of diffuse large B-cell lymphoma with multifocal cardiac involvement identified by total body 18FDG positron emission tomography performed at disease staging.

Addressing Post-Acute COVID-19 Syndrome in Cancer Patients, from Visceral Obesity and Myosteatosis to Systemic Inflammation: Implications in Cardio-Onco-Metabolism.

Cardiovascular disease and cancer are the two leading causes of morbidity and mortality in the world. The emerging field of cardio-oncology described several shared risk factors that predispose patients to both cardiovascular disease and cancer. Post-acute COVID-19 syndrome is a chronic condition that occurs in many patients who have experienced a SARS-CoV-2 infection, mainly based on chronic fatigue, sedentary lifestyle, cramps, breathing difficulties, and reduced lung performance. Post-acute COVID-19 exposes patients to increased visceral adiposity, insulin resistance, myosteatosis, and white adipose tissue content (surrounded by M1 macrophages and characterized by a Th1/Th17 phenotype), which increases the risk of cardiovascular mortality and cancer recurrence. In this review, the main metabolic affections of post-acute COVID-19 syndrome in cancer patients at low and high risk of cardiomyopathies will be summarized. Furthermore, several non-pharmacological strategies aimed at reducing atherosclerotic and cardiac risk will be provided, especially through anti-inflammatory nutrition with a low insulin and glycemic index, appropriate physical activity, and immune-modulating bioactivities able to reduce visceral obesity and myosteatosis, improving insulin-related signaling and myocardial metabolism.

Prognostic stratification by conventional echocardiography of patients with aortic stenosis: the "CAIMAN-ECHO score".

BACKGROUND AND AIM: Surgery is not recommended in asymptomatic patients with aortic stenosis (AS). However, prognosis of these patients is worse than retained. We built a simple score (named by the acronym "CAIMAN") for stratifying asymptomatic patients with AS according to the different risk for cardiovascular events. MATERIAL AND METHODS: Data from 141 patients with moderate-to-severe AS followed up for 36 months were analyzed. The end point "outcome" was defined as death of all causes or aortic valve replacement imposed by symptoms or hospital admission for myocardial infarction and/or heart failure. The score was validated in 143 patients prospectively recruited in 2 different centers. RESULTS: The 40 events occurred in the original cohort were associated with higher aortic transvalvular peak jet velocity, calcium score, and observed/predicted left ventricular (LV) mass ratio. Based on the hazard ratios of Cox analysis, the score was calculated as follows: calcium score 1-3 = 1 point, 4 = 6 points; transvalvular peak jet velocity ≤3.6 m/sec = 1 point, 3.6 m/sec = 3 points, observed/predicted LV mass ratio ≤110% = 1 point, >110% = 3 points. After a mean period of 28 ± 18 months, event-free survival was 18%, 42%, 91%, and 96% in the 4 quartiles of echo score. The accuracy of the score in predicting events was 84% and 77% (P = 0.09) in the original and validation cohort, respectively. CONCLUSIONS: The CAIMAN-ECHO score is a simple and feasible tool useful for an accurate prognostic stratification of patients with asymptomatic moderate-to-severe AS.

Combined circumferential and longitudinal left ventricular systolic dysfunction in patients with type 2 diabetes mellitus without myocardial ischemia.

BACKGROUND/OBJECTIVE: Left ventricular (LV) circumferential or longitudinal shortening may be impaired in patients with type 2 diabetes mellitus (DM). In the present study, patients with type 2 DM without myocardial ischemia and combined impairment of circumferential and longitudinal (C+L) shortening were studied to assess the prevalence and factors associated with this condition. METHODS: Data from 386 patients with type 2 DM enrolled in the SHORTening of midWall and longitudinAl left Ventricular fibers in diabEtes study were analyzed. One hundred twenty healthy subjects were used to define C+L dysfunction. Stress-corrected midwall shortening and mitral annular peak systolic velocity were considered as indexes of C+L shortening and classified as low if <89% and <8.5 cm/s, respectively (10th percentiles of controls). RESULTS: Combined C+L dysfunction was detected in 66 patients (17%). The variables associated with this condition were lower glomerular filtration rate (OR 0.98 [95% CI 0.96 to 0.99], greater LV mass (OR 1.05 [95% CI 1.02 to 1.08]), high pulmonary artery wedge pressure (OR 1.23 [95% CI 1.04 to 1.44]) and mitral annular calcifications (OR 3.35 [95% CI 1.71 to 6.55]). Considering the entire population, the relationship between stress-corrected midwall shortening and peak systolic velocity was poor (r=0.20), and the model was linear. The relationship was considerably closer and nonlinear in patients with combined C+L dysfunction (r=0.61; P<0.001), having the best fit by cubic function. CONCLUSIONS: Combined C+L dysfunction was present in one-sixth of patients with type 2 DM without myocardial ischemia. This condition was associated with reduced renal function, worse hemodynamic status and structural LV abnormalities, and may be considered a preclinical risk factor for heart failure.

[Hormone therapy, cardio-metabolic profile, and cardiotoxicity. Still a dark side of cardio-oncology - Part 2: Prostate cancer]. / Terapia ormonale, assetto cardio-metabolico e cardiotossicità. Il lato ancora oscuro della cardioncologia ­ Parte 2: Tumore della prostata.

Hormone therapies (HTs) with anti-androgenic properties are a cornerstone for the treatment of prostate cancer (PC) and have significantly improved the survival of patients, though exposing them to a higher risk of cardiovascular diseases (CVDs), which represent a major cause of morbidity and mortality. This occurs due to the high average age of patients undergoing HT for PC, an age group in which CVDs have a high prevalence and incidence, and due to the type and duration of HTs that are increasingly effective but at the same time more aggressive towards cardiovascular health. Recent evidence from the real world suggests, however, that the cardiometabolic risk is widely underestimated and undertreated with significant impact also on the oncological prognosis. In the light of the results of the PRONOUNCE study, in this review it is emphasized the need for a multidisciplinary management of patients with PC who are candidate for or treated with HT by implementing a personalized treatment program in accordance with the current European guidelines on CVD prevention.