Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma.

Compared to other patients suffering from hematological malignancies, classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients have a long life expectancy when in complete remission at the end of first, or sometimes second, line treatments [...].

Cancer-Associated Thrombosis: Not All Low-Molecular-Weight Heparins Are the Same, Focus on Tinzaparin, A Narrative Review.

Cancer-associated thrombosis (CAT) is the second main cause of cancer death with high related mortality and morbidity, leading to anticancer agent delays and interruptions. The recommended therapy, low-molecular-weight heparin (LMWH), however, is burdensome for patients and costly for society, as treatment should last until cancer is no longer active, even indefinitely. Tinzaparin is a manageable, efficient, safe, and cost-effective option. Compared to the other LMWHs, advantages are single-daily dose and safety in the elderly and those with renal impairment (RI). The purpose of this review is to critically discuss recent data on its efficacy and safety in CAT.

Edoxaban: front-line treatment for brachiocephalic vein thrombosis in primitive mediastinal seminoma: A case report and literature review.

RATIONALE: Venous thromboembolism is a feared frequent complication of cancer with a 2-way relationship. Low molecular weight heparin is the mainstay of treatment. The use of direct oral anticoagulants is supported by established evidence for the treatment of deep vein thrombosis also in active cancer and they are prioritized over low molecular weight heparin for cancer-associated thrombosis according to current guidelines. However, upper limb deep vein thrombosis is poorly studied with scant data on the use of direct oral anticoagulants in noncatheter-related deep vein thrombosis. We report the case of a patient with noncatheter-related deep vein thrombosis and a rare tumor site effectively and safely treated with a direct oral anticoagulant, edoxaban, after lack of efficacy with low molecular weight heparin. PATIENT CONCERNS: A 35-year-old man with primitive mediastinal seminoma presented at our Cardio-Oncology Unit for prechemotherapy assessment. DIAGNOSIS: Persistent brachiocephalic deep vein thrombosis, despite full-dose enoxaparin, was detected at ultrasonography. INTERVENTION: We decided to switch the anticoagulant treatment from enoxaparin to edoxaban. OUTCOME: The 3-month ultrasonography showed almost total regression of the deep vein thrombosis without any adverse effects and a good patient compliance. LESSONS: We conducted a literature review on upper limb deep vein thrombosis, since its management is challenging due to inconsistency of evidence. This report highlights the benefits of direct oral anticoagulants compared to low molecular weight heparins in cancer-associated thrombosis therapy in terms of efficacy, safety and ease of use.

Echocardiography Monitoring during Anthracycline Administration in Hodgkin and Non-Hodgkin's Lymphoma: The Tei Index Evaluation.

Anthracyclines are widely employed in lymphoma's chemotherapy and has been shown to induce heart failure. Echocardiographic parameters of left ventricular (LV) systolic function are usually used to monitor the cardiac side effects during and after anthracyclines treatment. The measurement of theTei index could anticipate the onset of LV dysfunction. The aim of this study was to evaluate the performance of the delta Tei index for the early detection of cardiac toxicity in a prospective population of anthracycline-treated lymphoma patients. Our preliminary data suggest that the Tei index may predict the risk for cardiotoxicity in this subset of patients earlier than LV ejection fraction alteration.

Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi.

Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche "Mario Negri", conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease.

Renal Venous Pattern: A New Parameter for Predicting Prognosis in Heart Failure Outpatients.

AIM OF THE STUDY: In chronic heart failure (CHF) patients, renal congestion plays a key role in determining the progression of renal dysfunction and a worse prognosis. The aim of this study was to define the role of Doppler venous patterns reflecting renal congestion that predict heart failure progression. METHODS: We enrolled outpatients affected by CHF, in stable clinical conditions and in conventional therapy. All patients underwent a clinical evaluation, routine chemistry, an echocardiogram and a renal echo-Doppler. Pulsed Doppler flow recording was performed at the level of interlobular renal right veins in the tele-expiratory phase. The venous flow patterns were divided into five groups according to the fluctuations of the flow. Type A and B were characterized by a continuous flow, whereas type C was characterized by a short interruption or reversal flow during the end-diastolic or protosystolic phase. Type D and E were characterized by a wide interruption and/or reversal flow. The occurrence of death and/or of heart transplantation and/or of hospitalization due to heart failure worsening was considered an event during follow-up. RESULTS: During a median follow-up of 38 months, 126 patients experienced the considered end-point. Venous pattern C (HR 4.04; 95% CI: 2.14⁻7.65; p < 0.001), pattern D (HR 7.16; 95% CI: 3.69⁻13.9; p < 0.001) and pattern E (HR 8.94; 95% CI: 4.65⁻17.2; p < 0.001) were all associated with events using an univariate Cox regression analysis. Moreover, both the presence of pattern C (HR: 1.79; 95% CI: 1.09⁻2.97; p: 0) and of pattern D or E (HR: 1.90; 95% CI: 1.16⁻3.12; p: 0.011) remained significantly associated to events using a multivariate Cox regression analysis after correction for a reference model with an improvement of the overall net reclassification index (0.46; 95% CI 0.24⁻0.68; p < 0.001). CONCLUSIONS: Our findings demonstrate the independent and incremental role of Doppler venous patterns reflecting renal congestion in predicting HF progression among CHF patients, thus suggesting its possible utility in daily clinical practice to better characterize patients with cardio-renal syndrome.

The Renal Arterial Resistance Index Predicts Worsening Renal Function in Chronic Heart Failure Patients.

BACKGROUND/AIM: The renal arterial resistance index (RRI) is a Doppler measure, which reflects abnormalities in the renal blood flow. The aim of this study was to verify the value of RRI as a predictor of worsening renal function (WRF) in a group of chronic heart failure (CHF) outpatients. METHODS: We enrolled 266 patients in stable clinical conditions and on conventional therapy. Peak systolic velocity and end diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow, and RRI was calculated. Creatinine serum levels were evaluated at baseline and at 1 year, and the changes were used to assess WRF occurrence. RESULTS: During follow-up, 34 (13%) patients showed WRF. RRI was associated with WRF at univariate (OR: 1.13; 95% CI: 1.07-1.20) as well as at a forward stepwise multivariate logistic regression analysis (OR: 1.09; 95% CI: 1.03-1.16; p = 0.005) including the other univariate predictors. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts the WRF in CHF outpatients. Its possible role in current clinical practice to better define the risk of cardiorenal syndrome progression is strengthened.

Right Ventricular Longitudinal Strain Measures Independently Predict Chronic Heart Failure Mortality.

The assessment of right ventricular (RV) function still remains a challenge. Two-dimensional (2D) speckle tracking has recently been proposed to evaluate right ventricular function by analyzing myocardial deformation. The aim of this study was to evaluate the role of 2D systolic strain measures of RV in predicting mortality in patients with chronic heart failure (HF). We enrolled 332 outpatients in a stable clinical condition and in conventional therapy. A right ventricular-focused four-chamber view was analyzed by 2D speckle tracking to evaluate the global longitudinal strain of RV (RV-GLS) and the strain of RV free wall (RV-fwLS). During a mean follow-up of 36 ± 26 months, 64 patients died. Both RV-GLS and RV-fwLS were associated with all-cause mortality in univariate (HR: 1.16; 95% CI: 1.10-1.23; P < 0.001; C-index: 0.72; and HR: 1.10; 95% CI: 1.06-1.15; P < 0.001; C-index: 0.68, respectively) as well as multivariate analysis (HR: 1.13; 95% CI: 1.05-1.21; P:0.001; C-index: 0.85; and HR: 1.07; 95% CI: 1.02-1.12; P:0.004; C-index: 0.84, respectively). In conclusion, our findings demonstrate the role of RV 2D strain measures to independently predict mortality. These data highlight the clinical usefulness of this echocardiographic approach in the daily management of HF outpatients.

The independent association between altered renal arterial resistance and loop diuretic dose in chronic heart failure outpatients.

BACKGROUND: In chronic heart failure (CHF) patients there is a wide variability in the minimal effective diuretic dose. The aim of this study is to evaluate whether renal resistance index (RRI) is associated to baseline diuretic dose and the changes at one year. METHODS AND RESULTS: 250 outpatients in a stable condition and in conventional therapy were enrolled. Baseline RRI was calculated by renal arterial Doppler. The total daily dose of loop diuretics was assessed at baseline and after one year. High diuretic dose (HDD) was defined as a daily furosemide equivalent dose > 100 mg. RRI was independently associated with baseline HDD at univariate (OR 1.39; 95% CI: 1.233-1.58; p < 0.001) and multivariate analysis (OR 1.27; 95% CI: 1.09-1.49; p: 0.002) after correction for other univariate predictors (age, NYHA class, left ventricular ejection fraction, tricuspid annulus peak of systolic excursion, NT-proBNP, glomerular filtration rate by EPI formula and central venous pressure). Moreover, baseline RRI was independently associated to one year stable increase in loop diuretic dose at univariate and multivariate regression analyses. CONCLUSIONS: RRI is independently associated with high dose loop diuretics and their increase during a mid-term follow-up thus suggesting its usefulness in detecting an altered diuretic response in CHF outpatients.

Modulation of cardiac cytochrome P450 in patients with heart failure.

INTRODUCTION: There is increasing evidence that cytochrome P450 (CYP) plays a role in the onset, progression and prognosis of cardiovascular disease (CVD), in particular, heart failure (HF). The importance of CYP enzymes in cardiovascular physiology derives from their ability to metabolize arachidonic acid to epoxyeicosatrienoic and hydroxyeicosatetraenoic acids, which are involved in the maintenance of cardiovascular health, including the regulation of vascular tone, cardiac ion channels and heart contractility. Moreover, CYP plays a central role in the Phase I metabolism of drugs and other xenobiotics. Inter-individual variability in expression and function of CYP enzymes is a major factor accounting for individual susceptibility to drug response. AREAS COVERED: This review focuses on current knowledge of the role of CYP enzymes and their metabolites in the pathogenesis of CVD, in particular, HF. The role of CYP enzymes in affecting individual response to cardiovascular drugs is also discussed. The literature search was performed using the PubMed database. EXPERT OPINION: More research is needed to elucidate the mechanisms by which CYP affects the pathophysiology of HF and also the mechanism by which HF alters cardiac and hepatic CYP enzymes.

The renal arterial resistance index: a marker of renal function with an independent and incremental role in predicting heart failure progression.

AIMS: The renal arterial resistance index (RRI) is a measure of renal blood flow obtained by Doppler ultrasonography, which has been demonstrated to reflect both vascular and parenchymal renal abnormalities. The aim of the study was to evaluate clinical correlates and the prognostic relevance of RRI in a group of patients affected by chronic heart failure (CHF). METHODS AND RESULTS: We enrolled 250 CHF outpatients in a stable clinical condition and receiving conventional therapy. Peak systolic velocity and end-diastolic velocity of a segmental renal artery were obtained by pulsed Doppler flow. Then the RRI was calculated. Standard renal function assessment was obtained by the measurement of creatinine serum levels and the estimation of the glomerular filtration rate (GFR). During follow-up (21.4 ± 11.3 months), 41 patients experienced heart failure progression (hospitalization and/or heart transplantation and/or death due to worsening heart failure). Considered as a continuous variable, RRI was associated with events at univariate [hazard ratio (HR) 1.14; 95% confidence interval (CI) 1.09-1.19; P < 0.001] as well as at multivariate Cox regression analysis (HR 1.08; 95% CI 1.02-1.13; P = 0.004) after correction for independent predictors of the reference model. When the RRI was added to the reference model including GFR, a significant improvement of reclassification according to both category-free net reclassification improvement (NRI, 47%; 95% CI 13-80%; P = 0.006) and integrated discrimination improvement (IDI, 0.034; 95% CI 0.006-0.061; P = 0.016) was observed. CONCLUSIONS: Quantification of arterial renal perfusion provides a new parameter that independently predicts CHF patient outcome, thus strengthening its possible role in current clinical practice in order to better characterize renal function and stratify patients' prognosis.

Independent role of left ventricular global longitudinal strain in predicting prognosis of chronic heart failure patients.

AIMS: To evaluate the independent prognostic role of two-dimensional (2D) strain measures reflecting global longitudinal left ventricular (LV) systolic function in outpatients affected by chronic heart failure (CHF). METHODS AND RESULTS: Global longitudinal LV systolic strain (GLS) was assessed in 308 outpatients affected by CHF, by analyzing standard views with 2D speckle tracking technique. During a mean follow-up of 26 ± 13 months 37 patients died (29 due to cardiovascular causes), 10 patients underwent heart transplantation, and 75 patients experienced at least 1 episode of hospitalization due to acute decompensated heart failure (ADHF). Thirty-one patients without a history of major ventricular arrhythmic events experienced the occurrence of ventricular fibrillation and/or tachycardia or sudden death was observed. Multivariate Cox regression analysis showed that GLS was significantly associated with all-cause mortality (HR: 1.15; 95%CI: 1.02-1.30; P: 0.026), cardiovascular death (HR: 1.20; 95%CI: 1.04-1.39; P: 0.011), cardiovascular death or heart transplantation (HR: 1.24; 95%CI: 1.09-1.41; P: 0.001), ADHF-related hospitalizations (HR: 1.15; 95%CI: 1.05-1.25; P: 0.003), and arrhythmic events (HR: 1.17; 95%CI: 1.03-1.33; P: 0.018). CONCLUSIONS: Quantifying LV longitudinal systolic function in CHF outpatients on the basis of 2D speckle tracking analysis provides a new parameter that independently predicts patient outcome, thus, strengthening its possible role in current clinical practice.

Incidence and prevalence of hypothyroidism in patients affected by chronic heart failure: role of amiodarone.

BACKGROUND: It has been demonstrated that hypothyroidism can lead to significant hemodynamic alterations favoring the onset of chronic heart failure (CHF) as well as its progression. Furthermore, amiodarone, an iodine-containing antiarhythmic drug frequently used in CHF patients, is often the cause of primary hypothyroidism. AIM OF THE STUDY: To define the prevalence and incidence of hypothyroidism in a group of CHF outpatients in stable clinical conditions, with particular reference to the role of amiodarone therapy. RESULTS: Among the 422 enrolled patients (326 males, aged 65±12 years), 51 (12%) had a previous diagnosis of hypothyroidism while 21 (5%) were newly diagnosed at the enrolment. Then, the overall prevalence of hypothyroidism at the first evaluation was 17%and, as expected, it was significantly higher in females than males (33% vs 13%; p < 0.001). During follow-up (median 28 months) hypothyroidism occurred in further 19 patients (incidence rate: 26/1000/year) and it was mainly attributable to amiodarone therapy. Considering all together the hypothyroid patients, either those affected by thyroid failure at the enrolment than those developing hypothyroidism during the follow-up, levothyroxine therapy was continued or started in 69% of them; however, normal serum TSH values were obtained only in 76% of treated cases (mean levothyroxine dose: 69±44 mcg/day). In any case, in the group of patients affected by hypothyroidism a significantly greater occurrence of heart failure progression was observed. CONCLUSIONS: Hypothyroidism, especially the subclinical form, frequently occurs in patients affected by CHF receiving amiodarone therapy. Given the unfavorable impact of hypothyroidism on the progression and prognosis of CHF, and the opportunity to adequately manage thyroid failure by means of levothyroxine replacement therapy without the need to withdraw amiodarone, we recommend regular testing of thyroid function in CHF patients, in particular in those submitted to amiodarone therapy, in order to early diagnose a condition of hypothyroidism and titrate substitutive treatment.

Altered two-dimensional strain measures of the right ventricle in patients with Brugada syndrome and arrhythmogenic right ventricular dysplasia/cardiomyopathy.

AIMS: Brugada syndrome (BrS) is an inherited channelopathy that can be characterized by mild right ventricular (RV) abnormalities that are not detectable with conventional echocardiography. The aim of this study was to evaluate the presence of RV abnormalities in BrS patients when compared with controls and a group of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) using two-dimensional (2D) strain analysis. METHODS AND RESULTS: We enrolled 25 BrS, 15 ARVD/C patients, and 25 controls. Right and left ventricular dimension and systo-diastolic function were evaluated by conventional echocardiography. Longitudinal systolic strain (sS) peak, systolic and early diastolic strain rate of lateral RV segments were evaluated by 2D speckle tracking analysis. Left ventricle global and segmental strain measures were also evaluated. A reduced basal or mid-RV lateral sS were the parameters mostly associated with both BrS and ARVD/C. In BrS patients the minimum sS observed in these segments was significantly lower than that of controls (-28.9±3.2% vs. -32.3±3.2%, P: 0.002) but significantly greater than that evaluated in ARVD/C patients (-24.6±6.7%, P<0.001 both vs. BrS and controls). No differences were found between the BrS and the control group when left ventricular strain measures were analysed. CONCLUSION: By 2D strain technique it is possible to observe mild abnormalities in RV systolic and diastolic function of BrS patients that are less pronounced than those observed in ARVD/C patients. These results help to better define the phenotypic characteristics of BrS patients and represent the basis for future studies aimed at testing their clinical usefulness in BrS patients.

Clinical correlates of endothelial function in chronic heart failure.

OBJECTIVE: There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF). DESIGN, SETTING, PATIENTS: We evaluated 60 CHF outpatients (age 62 ± 14 years; 49 males, NYHA class 2.2 ± 0.7, left ventricular ejection fraction, LVEF, 33 ± 8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions. MAIN OUTCOME MEASURES: The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value. RESULTS: As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p = 0.032) and diabetes mellitus (20 vs. 3%; p = 0.044), had a higher NYHA class (2.5 ± 0.5 vs. 1.9 ± 0.7; p < 0.001) and NT-proBNP (2,690 ± 3,690 vs. 822 ± 1,060; p = 0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63 ± 28 vs. 78 ± 25; p = 0.001) and LVEF (29 ± 8 vs. 37 ± 9; p = 0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p = 0.002). In a multivariate regression model (R (2) = 0.48; p < 0.001), FMD remained associated only with the NYHA class (p = 0.039) and diabetes mellitus (p = 0.024). CONCLUSIONS: This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.

Nitrate-potentiated head-up tilt testing in older patients: outcomes, hemodynamic responses and prodrome recognition.

BACKGROUND: To compare head-up tilt testing (HUT) outcomes and hemodynamic responses, and the prevalence and correlates of prodromes, in elderly and younger patients with suspected vasovagal syncope (VVS). METHODS: Consecutive outpatients with a history of recurrent unexplained syncope underwent HUT by being tilted to 70°; the test was potentiated by the administration of 300 µg of nitroglycerine after 20 minutes. Occurrence of VVS and hemodynamic responses during passive and nitroglycerine phases of HUT were evaluated; symptoms preceding HUT-induced syncope were recorded, together with heart rate and arterial blood pressure values. RESULTS: Four hundred and sixty of the 743 patients were HUT positive: 156 fainted during the unmedicated phase and 304 after nitroglycerine administration. The patients aged ≥65 years (n = 102) experienced VVS more frequently during the pharmacological stage of HUT; the overall rate of positive results was similar to that observed in the patients aged 36-64 years (n = 329) and only slightly lower than that observed in those aged ≤ 35 years (n = 312). In the older patients, who experienced fewer and mainly prodrome-free spontaneous syncopal episodes, HUT increased the number of premonitory symptoms, and there were no significant age-related differences in symptom prevalence or timing or the patients' hemodynamic characteristics. CONCLUSIONS: The rate of VVS induced by nitroglycerine-potentiated HUT is similar in elderly and younger patients. In the former, nitroglycerine-potentiated HUT significantly increases the prevalence of prodromes in comparison with spontaneous episodes, which suggests that it may be useful not only for diagnosis but also for patient counseling.