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Purpose of the Review Arterial hypertension (AH) is the most common cardiovascular (CV) risk factor in the community and in oncologic patients. It also represents the most important CV condition predisposing to anticancer treatment-related cardiotoxicity. This risk is heightened in the presence of cardiac AH-mediated organ damage (HMOD). Influence of AH and HMOD on the development of cardiotoxicity will be reviewed, with a focus on specific scenarios and implications for management of oncologic patients. Recent Findings Not adequately controlled AH before or during anticancer treatments and/or development of AH during or after completion of such therapies have detrimental effects on the clinical course of oncologic patients, particularly if HMOD is present. Summary As overlooking CV health can jeopardize the success of anticancer treatments, the goal for clinicians caring for the oncologic patient should include the treatment of AH and HMOD.

Background Recent studies have shown that the concentrations of growth differentiation factor 15 (GDF-15) increase after anthracycline administration and may be associated with cardiotoxicity during or shortly after treatment. The relation of GDF-15 with late-onset cardiotoxicity has far less been studied. Methods We examined GDF-15 levels across the spectrum of left ventricular (LV) function in a single-center cohort of adult patients who had received curative chemotherapy for Hodgkin lymphoma and underwent comprehensive cardiologic assessment including transthoracic echocardiography (TTE) as part of long-term follow-up. Plasma GDF-15 was measured by enzyme-linked immunosorbent assay, and the concentrations between TTE phenotypes were compared by unpaired Student's t test. The correlation between GDF-15 values and echocardiographic parameters was investigated by linear regression. Results 35 (18 males, 51%) patients were evaluated a median of 47 months (IQR 24-67) after doxorubicin-containing chemotherapy. The median age at the end of treatment and at the time of TTE was 35 years (IQR 28-50) and 40 years (IQR 32-56), respectively. All subjects had received ABVD with or without rituximab as a first-line treatment; 2 (6%) had also received mediastinal irradiation, 6 (17.4%) a second-line therapy, 2 (8.7%) a third-line treatment, and 8 (17.4%) had ultimately undergone bone marrow transplantation. None had a history of heart disease or atrial fibrillation, nor NYHA class ≥II. Body mass index was 24 ± 5 Kg/m2. Seven (20%) patients had hypertension, 9 dyslipidemia (26%), and 2 (6%) diabetes; 28 (80%) were prior or current smoker. Mean GDF-15 was 1132,9 ± 485,0 pg/mL. LV ejection fraction (LVEF) was always >50%; 3 (9%) subjects had global longitudinal strain (GLS) < -18%. Moreover, 7 (20%) had mild or moderate diastolic dysfunction, as defined by E/A ratio Conclusions Our results suggest that GDF-15 tracks with LV diastolic, rather than systolic, dysfunction years after anthracycline chemotherapy.

We reviewed frequency, microbiological pattern, predictors, and outcomes of early infections following transcatheter aortic valve replacement (TAVR).Five hundred thirty-nine patients who underwent successful TAVR at a single, high-volume center between January 2014 and December 2019 were enrolled. We defined early infections as occurring within 30-day from TAVR.Mean age was 83.5 ± 5.4 years; 230 (42.7%) patients were men. Median follow-up was 12.0 (5.7-18.3) months; 30-day and 1-year death rates were 8/539 (1.5%) and 30/539 (5.6%), respectively. Early infections occurred in 61/539 (11.3%) patients, of whom 2 had infections in two sites. Of the 63 infections, 10 were bloodstream infections (BSI), 5 urinary tract, 27 pulmonary (2 with sepsis), 6 access site infections, 1 enterocolitis, and 14 were clinically diagnosed (no specific site). We observed 31/63 (49.2%) microbiologically-documented infections: Gram+ bacteria were isolated in 12/31 (38.7%), Gram- in 17/31 (54.3%), both Gram+ and Gram- in 2/31 (6.5%); in thirty-two infections no specific pathogen could be isolated (clinically-documented infections). Early infections were more prevalent in patients who died within 30-day (8.2% vs. 0.6%, p0.001) or 1-year (14.8% vs. 4.4%, p0.001) from TAVR. At multivariable analysis, early infections were independently associated with 30-day (HR: 8.82, 95% CI: 1.11-19.83, p = 0.035) and 1-year mortality (HR: 2.10, 95%CI: 1.28-6.21, p = 0.041). The predictive value for 1-year mortality was maintained even restricting the analysis to documented infections only, or to more severe infections (BSI and pneumonia only) (all p0.05).Early infections occur in 1/10th of TAVR and are associated with increased short- and long-term mortality. Whereas a causal relationship between early infections and the risk of death cannot be unequivocally proven, careful surveillance of infected patients may improve TAVR results.

Peri-procedural myocardial injury (PPMI) is a common complication after transcatheter valve replacement (TAVR), often remaining clinically silent. The role of valve type on PPMI and the association between PPMI and mortality are still unclear. We sought to evaluate predictors and outcome of PPMI after TAVR, and the impact of self-expandable valve (SEV) vs. balloon-expandable valve (BEV) deployment on PPMI. Consecutive patients who underwent successful TAVR in a single-center from January 2014 to December 2019 were included. PPMI was defined according to a modified Valve Academic Research Consortium (VARC)-2 definition as a post-procedure elevation of troponin (with a peak value ≥ 15-times the upper-reference limit) p p = 0.011), and baseline ejection fraction (OR 1.05, 95% CI 1.02–1.07, p p = 0.488) or 1-year (p = 0.139) all-cause mortality were found. Independent predictors of 30-day mortality were increasing EUROSCORE II (HR 1.16 per score point, 95% CI 1.08–1.19, p p = 0.019), whereas EUROSCORE II (HR 1.08, 95% CI 1.04–1.13, p = 0.031) and acute kidney injury (HR 2.59, 95% CI 1.20–5.35, p = 0.020) were related to 1-year mortality. PPMI is frequent after TAVR, but it does not affect 30-day or 1-year all-cause mortality. SEV implantation is associated with an increased frequency of PPMI.

Heart failure symptoms, in particular dyspnea, may be difficult to frame in a patient with cancer. We report the case of an oncological patient whose dyspnea could have been attributable to various causes and whose management was challenging in the context of the coronavirus disease-2019 pandemic. (Level of Difficulty: Beginner.), Graphical abstract

The great therapeutical success achieved by oncology is counterbalanced by growing evidences of cardiovascular (CV) toxicity due to many antineoplastic treatments. Cardiac adverse events may cause premature discontinuation of effective oncologic treatments or occur as late events undermining the oncologic success. Arterial hypertension is both the most common comorbidity in cancer patients and a frequent adverse effect of anticancer therapies. A pre-existing hypertension is known to increase the risk of other cardiac adverse events due to oncologic treatments, in particular heart failure. Moreover, as a strict association between cancer and CV diseases has emerged over the recent years, various analyses have shown a direct relationship between hypertension and cancer incidence and mortality. Finally, many antineoplastic treatments may cause a rise in blood pressure (BP) values, particularly the novel anti VEGF agents, this possibly compromising efficacy of chemotherapy. Aim of this review is to revise the topic and the many aspects linking arterial hypertension and cancer, and to provide a comprehensive and practical guide of the current treatment approaches.

Acute kidney injury (AKI) may complicate transcatheter aortic valve replacement (TAVR) leading to higher mortality. The relationship between AKI, obesity, and mortality, however, is controversial. We sought to investigate the impact of body habitus on the prognostic value of AKI in TAVR.Among the 645 patients who underwent successful TAVR in a single high-volume centre, we retrospectively evaluated the association between AKI-TAVR and 30-day, 6-month, and 1-year mortality, and whether this relationship was affected by BMI. AKI was defined according to the Valve Academic Research Consortium-2 criteria. Patients were categorized into three groups by BMI: low-to-normal weight (25 kg/m2), overweight (25-30 kg/m2), obese (30.0 kg/m2).Three-hundred and twenty-four (50.2%) patients were low-to-normal weight, 223 (34.6%) overweight, and 98 (15.2%) obese. AKI occurred in 141 (21.9%), similarly across BMI groups. Thirty-day, 6-month, and 1-year mortality rates were 2.2, 3.7, and 7.9%, without differences across BMI groups. Among patients who developed AKI-TAVR, 30-day (8.7 vs. 2.0 vs. 0.0%), 6-month (13.0 vs. 6.1 vs. 4.3%), and 1-year (20.3 vs. 12.2 vs. 4.3%) mortality showed a decreasing trend across increasing BMI categories (all P 0.05); the same trend was not observed for patients without AKI-TAVR. In multivariate models, AKI was associated with 30-day [odds ratio (OR): 2.46, 95% confidence interval (CI): 1.70-8.67], 6-month (OR: 2.75, 95% CI: 1.32-7.59), and 1-year mortality (OR: 1.84, 95% CI: 1.22-3.71, all P 0.05). The interaction between AKI and BMI, when added to the models, was consistently significant (all P 0.05).Higher BMI is associated with better survival in TAVR patients who develop AKI.

Background: the European Society of Cardiology Heart Failure Association (HFA) together with the International Cardio-Oncology Society (ICOS) proposed charts for baseline CV risk assessment of cancer patients scheduled to receive anthracyclines and anti-human epidermal growth factor receptor-2 (HER2) agents. Methods: We investigated HFA/ICOS risk stratification, prescriptions of cardioactive drugs, and occurrence of CV events in a multicentric breast cancer (BC) cohort from 3 Italian Outpatient Cardio-Oncology Clinics. Results: 373 BCE patients who underwent a baseline Cardio-Oncologic evaluation were included, of whom 202 scheduled to receive anthracyclines and 171 anti-HER2. Mean age was 60 ± 12 years and 49% of BC patients had ≥2 CV risk factors. In the anthracyclines group, 51% were at low-risk, 43% at medium-risk and 6% at high-risk; while in the anti-HER2 group, 27% patients were at low-risk, 58% at medium-risk and 15% at high-risk. In both groups, a medium-to-high risk was associated with use of cardioactive therapies (p

We read with interest the elegant paper by Jones et al. [(1)][1], investigating progression from stage A to stage B heart failure (HF) after potentially cardiotoxic chemotherapies. Given the known influence of cardiovascular risk factors (CVRF) on the development of cardiotoxicity [(2,3)][2], the

Creatine is of paramount importance for maintaining and managing cellular ATP stores in both physiological and pathological states. Besides these "ergogenic" actions, it has a number of additional "pleiotropic" effects, e.g., antioxidant activity, neurotransmitter-like behavior, prevention of opening of mitochondrial permeability pore and others. Creatine supplementation has been proposed for a number of conditions, including neurodegenerative diseases. However, it is likely that creatine's largest therapeutic potential is in those diseases caused by energy shortage or by increased energy demand; for example, ischemic stroke and other cerebrovascular diseases. Surprisingly, despite a large preclinical body of evidence, little or no clinical research has been carried out in these fields. However, recent work showed that high-dose creatine supplementation causes an 8-9 % increase in cerebral creatine content, and that this is capable of improving, in humans, neuropsychological performances that are hampered by hypoxia. In addition, animal work suggests that creatine supplementation may be protective in stroke by increasing not only the neuronal but also the endothelial creatine content. Creatine should be administered before brain ischemia occurs, and thus should be given for prevention purposes to patients at high risk of stroke. In myocardial ischemia, phosphocreatine has been used clinically with positive results, e.g., showing prevention of arrhythmia and improvement in cardiac parameters. Nevertheless, large clinical trials are needed to confirm these results in the context of modern reperfusion interventions. So far, the most compelling evidence for creatine and/or phosphocreatine use in cardiology is as an addition to cardioplegic solutions, where positive effects have been repeatedly reported.

Background: Patients developing cancer treatment-related left ventricular dysfunction (CTrLVD) require a prompt therapy. Hypotension, dizziness, and fatigue often limit the use of angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and β-blockers (BB) in cancer patients who may already be afflicted by these symptoms. Ivabradine is a heart rate-lowering drug that does not cause hypotension and may be used in heart failure with reduced left ventricular ejection fraction (LVEF). Objective: The aim of this paper was to investigate the role of ivabradine to treat CTrLVD. Methods: A retrospective analysis in a cohort of 30 patients with CTrLVD (LVEF < 50%) receiving ivabradine on top of the maximal tolerated dose of ACEi/ARB and BB was performed. We evaluated cardiovascular treatment, oncologic treatment, LVEF, functional class (New York Heart Association [NYHA]), and fatigue during the study period. Results: Ivabradine was initially started at the dose of 2.5 mg/b.i.d. in most patients and then carefully titrated. Hypotension (70%) and fatigue (77%) were the main causes limiting the treatment with ACEi/ARB and BB. After a mean follow-up of 6.5 months, LVEF increased from 45.1% (SD = 6.4) to 53.2% (SD = 3.9; p < 0.001). When patients were analyzed according to the type of cancer therapy, no difference in LVEF changes across the groups was found. NYHA class ameliorated in 11 patients, while fatigue improved in 8 patients. No serious cardiovascular side effects were reported. Conclusions: The ability to improve symptoms and LVEF in unfit cancer patients makes ivabradine a reasonable pharmacological tool for treating CTrLVD.

Background Rare cases of severe myocarditis are reported during treatment with nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the diagnostic workup of many cardiac disorders, including myocarditis. This study investigates the role of troponin to assess cardiac involvement during nivolumab therapy for non-small cell lung cancer (NSCLC). Materials and Methods We evaluated 59 NSCLC patients, analyzing serum samples collected within a translational research study. Troponin above the upper normal limit (0.046 ng/mL) was defined as Tn+, whereas normal but detectable troponin (0.015–0.045) was defined as Tndet. Troponin alterations were interpreted on the grounds of the following elements: peak values and time curve, cardiac comorbidities, signs and symptoms coincident to troponin elevation, ECG, echocardiography, and disease progression. Results No patient had cardiovascular events. Among 362 available blood samples, Tn+ (max 0.317 ng/mL) was found in 13 determinations belonging to 6 patients. Seven other patients had isolated Tndet. In five patients, Tn+ was attributed to cardiac comorbidities, disease progression, or worsening clinical status. One patient without cardiac history and in good clinical condition had a sustained troponin increase—soon after the start of therapy—and after careful evaluation of all relevant elements, it was interpreted as a marker of nivolumab-related subclinical myocarditis. Conclusion Tn+ may occur in NSCLC patients treated with nivolumab, but in most cases it does not indicate nivolumab cardiotoxicity. In some cases, however, a careful interpretation of troponin alteration, especially at the beginning of therapy, enables identification of subclinical myocarditis, thus allowing early cardiac treatment. Implications for Practice Myocarditis is a rare but serious adverse event of immune checkpoint blockade with nivolumab, which needs to be recognized as soon as possible. This article suggests that troponin, a user-friendly biomarker of myocardial cytotoxicity, might be useful for early detection of immune-mediated myocarditis. However, because troponin abnormalities might also be related to a number of conditions capable of causing myocardial oxygen demand-supply mismatch, a careful cardiac assessment should be performed in non-small cell lung cancer patients in order to properly interpret any troponin increase. According to the available evidence, monitoring troponin during the first weeks of treatment can be considered reasonable.

Background Doxorubicin (DOX)-based chemotherapy for Hodgkin lymphoma (HL) yields excellent disease-free survival, but poses a substantial risk of subsequent left ventricular (LV) dysfunction and heart failure, typically with delayed onset. At the cellular level, this cardiotoxicity includes deranged cardiac glucose metabolism. Methods By reviewing the hospital records from January 2008 through December 2016, we selected HL patients meeting the following criteria: ≥ 18 year-old; first-line DOX-containing chemotherapy; no diabetes and apparent cardiovascular disease; 18-fluoro-deoxyglucose positron emission tomography (18FDG-PET) scans before treatment (PETSTAGING), after 2 cycles (PETINTERIM) and at the end of treatment (PETEOT); at least one echocardiography ≥ 6 months after chemotherapy completion (ECHOPOST). We then evaluated the changes in LV 18FDG standardized uptake values (SUV) during the course of DOX therapy, and the relationship between LV-SUV and LV ejection fraction (LVEF), as calculated from the LV diameters in the echocardiography reports with the Teicholz formula. Results Forty-three patients (35 ± 13 year-old, 58% males) were included in the study, with 26 (60%) also having a baseline echocardiography available (ECHOPRE). LV-SUV gradually increased from PETSTAGING (log-transformed mean 0.20 ± 0.27) to PETINTERIM (0.27 ± 0.35) to PETEOT (0.30 ± 0.41; P for trend

Cancer immunotherapy has become a well-established treatment option for some cancers after the development of a family of drugs targeting the so-called immune checkpoints, such as CTLA4 and PD-1 with PD-L1. These co-receptors/ligands inhibit the activation of T-cell, thus preventing an excessive inflammatory response. Tumors exploit these pathways to induce immune tolerance to themselves. Thus, the main effect of checkpoint-blocking drugs is to awake an immune response primarily directed against cancer cells. Nonetheless, as the immune response elicited by these drugs is not completely tumor-specific, their use may actually cause several adverse effects, including adverse cardiovascular effects. In this review, we will discuss the principles and potentiality of immunotherapy for cancer treatment, the experimental and clinical data on the role of CTLA4 and PD-1 with PD-L1 as immune-checkpoints in the cancer environment and in the cardiovascular system, and strategies aimed at preventing possible cardiovascular adverse effects of immune-checkpoint blockers.

Oncologists require the intervention of a cardiologist to prevent, identify, and treat the cardiovascular complication related to cancer and cancer treatment. In the near future, the need for a cardiologic consultation for cancer patients might increase. This could be related to epidemiological consideration

The oncologist may require the help of the cardiologist for different reasons. Sometimes he suspects a cardiovascular problem, in general he wants to reduce complications of a cardio-toxic treatment, and, in most cases, he will find useful to have a “portrait” of the patient’s actual cardiovascular status.

Background: HSCT has greatly improved the prognosis of patients affected by hematological malignancies leading to more long-term survivors. However, long-term survivors are at increased risk of developing complications; cardiovascular complications are relatively rare but, on the other hand, it seems quite common to develop cardiovascular risk factors like: arterial hypertension (AH), diabetes, dyslipidemia. Aims of the study: to observe the incidence and outcome of patients developing cardiovascular risk factors (CVRF) and cardiovascular events (CVE) after allo-HSCT, eventually identifying patient and HSCT-related risk factors for CVE (CVE predictors). Materials and methods: We retrospectively analyzed 300 patients undergoing allo-HSCT from January 2006 to December 2009. Patients were considered long-term survivors and suitable for the analysis if they were alive at 2 years after HSCT. Following variables were recorded: diagnosis, sex, age at time of HSCT, comorbidities and pre-existing risk factors, BMI, previous chemotherapy with anthracyclines, donor type, disease status at time of HSCT, conditioning regimens with or without total body irradiation (TBI), onset of acute or chronic graft versus host disease (aGVHD and cGvHD), treatment with high doses corticosteroids after HSCT. We observed incidence and outcome of early (within 2 years) and late (after 2 years) CVRF and CVE in long-term survivors; CVE were divided in non-serious (grade1-2) and serious (grade 3-4) if they required or not hospitalization. Dichothomius variables were compared with Chi-Square test or Fisher's exact test. Continuous variables were compared with Student's T-Test. Median Follow-Up duration was estimated with Kaplan Meier reverse survival method. Multiple linear regression models were built for multivariate analysis of CVE incidence. A two-sided p value Results: 4 of 300 patients died of acute heart failure within 2 years from HSCT. 149 patients were alive at least 2 years after HSCT, and 125 patients (83%) were alive at the time of last follow-up, with a median follow-up of 2384 days (range 722-3098) and a median age of 40 years (range 15-72). Overall crude mortality was 24/ 149 (17%), of whom 16 patients dying of disease recurrence (66%) and 8 patients (34%) dying due to non-relapse causes (Non Relapse Mortality, NRM). Non-serious CVE were observed in 42 patients (28%), whereas serious CVE were reported in 23 cases (15%; 5 acute coronary syndrome, 4 heart failure, 5 cardiac arrythmias, 5 cerebrovascular events, 2 aortic aneurism, 2 pericarditis), with 11 patients experiencing both. Regarding CVRF, post-HSCT AH was observed in 62 patients (42%), dyslipidemia in 124 pts (83%), diabetes in 29 pts (19%). In univariate analysis older age was associated with a higher risk of developing late diabetes (p 0.025), early and late AH (p Conclusions: Older allo-HSCT patients have an higher risk of developing any CVE and any CVRF than age-matched non-hematologic population; interestingly, prolonged treatment with high dose steroids also seems to play a role. CVE do not show nowadays a high impact on survival since they seems to be an uncommon complication of HSCT. Furthermore an increasing number of late CVRF has been observed, possibly leading to late cardiovascular events in the future and should therefore be monitored. Disclosures No relevant conflicts of interest to declare.