Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy.

BACKGROUND: Three types of anthracycline-induced cardiotoxicities are currently recognized: acute, early-onset chronic, and late-onset chronic. However, data supporting this classification are lacking. We prospectively evaluated incidence, time of occurrence, clinical correlates, and response to heart failure therapy of cardiotoxicity. METHODS AND RESULTS: We assessed left ventricular ejection fraction (LVEF), at baseline, every 3 months during chemotherapy and for the following year, every 6 months over the following 4 years, and yearly afterward in a heterogeneous cohort of 2625 patients receiving anthracycline-containing therapy. In case of cardiotoxicity (LVEF decrease >10 absolute points, and <50%), heart failure therapy was initiated. Recovery from cardiotoxicity was defined as partial (LVEF increase >5 absolute points and >50%) or full (LVEF increase to the baseline value). The median follow-up was 5.2 (quartile 1 to quartile 3, 2.6-8.0) years. The overall incidence of cardiotoxicity was 9% (n=226). The median time elapsed between the end of chemotherapy and cardiotoxicity development was 3.5 (quartile 1 to quartile 3, 3-6) months. In 98% of cases (n=221), cardiotoxicity occurred within the first year. Twenty-five (11%) patients had full recovery, and 160 (71%) patients had partial recovery. At multivariable analysis, end-chemotherapy LVEF (hazard ratio, 1.37; 95% confidence interval, 1.33-1.42 for each percent unit decrement) and cumulative doxorubicin dose (hazard ratio, 1.09; 95% confidence interval, 1.04-1.15 for each 50 mg/m(2) increment) were independent correlates of cardiotoxicity. CONCLUSIONS: Most cardiotoxicity after anthracycline-containing therapy occurs within the first year and is associated with anthracycline dose and LVEF at the end of treatment. Early detection and prompt therapy of cardiotoxicity appear crucial for substantial recovery of cardiac function.

Prevention of Atrial Fibrillation in High-risk Patients Undergoing Lung Cancer Surgery: The PRESAGE Trial.

OBJECTIVE: We performed a prospective, randomized clinical study to assess whether prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with elevated N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, reduces the incidence of postoperative atrial fibrillation. BACKGROUND: Postoperative atrial fibrillation is a well recognized complication after lung cancer surgery, with an incidence as high as 30%. Perioperative increase of NT-proBNP has been demonstrated to be a strong independent predictor of postoperative atrial fibrillation in this setting. METHODS: NT-proBNP concentration was measured 24 hours before surgery and soon after surgery in 1116 patients. Three hundred twenty (29%) patients showed a high NT-proBNP value and were enrolled: 108 were assigned to the metoprolol group, 102 to the losartan group, and 110 to the control group. RESULTS: Overall, the incidence of postoperative atrial fibrillation was 20% (n = 64); it was significantly lower in the metoprolol and losartan groups compared with the control group [6%, 12%, and 40%, respectively; relative risk 0.19, 95% confidence intervals (CIs), 0.09-0.37; P < 0.001 in the metoprolol group; and 0.29, 95% CI, 0.16-0.52; P < 0.001 in the losartan group). No significant difference was found when the metoprolol and losartan groups were directly compared (P = 0.21). CONCLUSIONS: A prophylactic treatment with metoprolol or losartan, initiated soon after lung cancer surgery in patients with high NT-proBNP levels, significantly reduced the occurrence of postoperative atrial fibrillation.

Incidence, Management, Prevention and Outcome of Post-Operative Atrial Fibrillation in Thoracic Surgical Oncology.

Atrial fibrillation (AF) is a common supraventricular arrhythmia, a recognized risk factor for ischemic stroke, as a potential driver for heart failure (HF). Cancer patients have an increased risk for AF, even not including any cancer-specific treatment, as surgery or chemotherapy. The mechanism is multifactorial, with inflammation and changes in autonomic tone as critical actors. Commonly, AF is a recurrent complication of the post-operative period in cancer surgery (especially thoracic). Recent papers confirmed a significant incidence of post-operative (non-cardiac surgery) AF (PAF), partially mitigated by the use of prophylactic (rate o rhythm control) treatments. A relevant difference, in terms of mean hospitalization time, emerges between patients developing PAF and those who do not, while long term impact remains a matter of debate, due to several potential confounding factors. Besides clinical predictors, structural (i.e., echocardiographic) and bio-humoral findings may help in risk prediction tasks. In this respect, pre-operative natriuretic peptides (NPs) concentrations are nowadays recognized as significant independent predictors of perioperative cardiovascular complications (including PAF), while elevated post-operative levels may further enhance risk stratification. The aim of the present paper is to trace the state of the art in terms of incidence, management, prevention, and outcome of PAF in the field of thoracic surgical oncology.

Acute kidney injury after lung cancer surgery: Incidence and clinical relevance, predictors, and role of N-terminal pro B-type natriuretic peptide.

BACKGROUND: Acute kidney injury (AKI) frequently occurs in several medical and surgical settings, and it is associated with increased morbidity and mortality. In patients undergoing lung cancer surgery, AKI has not been fully investigated. We prospectively evaluated the incidence, clinical relevance, and risk factors of AKI in patients undergoing lung cancer surgery. Moreover, we estimated the accuracy of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in the prediction of AKI. METHODS: Patients undergoing lung cancer surgery were included in the study. Plasma NT-proBNP was measured before and soon after surgery. Postoperative AKI was defined according to the Acute Kidney Injury Network (AKIN) classification. RESULTS: A total of 2179 patients were enrolled. Of them, 222 (10%) developed AKI and had a more complicated in-hospital clinical course (overall complication rate: 35% vs. 16%; P < 0.0001), and a longer hospital stay (10 ± 7 vs. 7 ± 4 days; P < 0.0001). The incidence of AKI increased in parallel with the extent of lung resection. Among the independent predictors of AKI, serum creatinine (area under the curve [AUC] 0.70 [95% CI 0.67-0.74]) and NT-proBNP (AUC 0.71 [95% CI 0.67-0.74]) provided the highest predictive accuracy, and their combination further significantly improved AKI prediction (AUC 0.74 [95% CI 0.71-0.77]). No difference in AKI prediction was observed between preoperative and postoperative NT-proBNP (P = 0.84). CONCLUSIONS: Acute kidney injury occurs in 10% of patients undergoing lung cancer surgery, and it is associated with a high incidence of postoperative complications. The risk of AKI can be accurately predicted by the combined evaluation of preoperative serum creatinine and NT-proBNP.

Strategies to prevent and treat cardiovascular risk in cancer patients.

Cardiotoxicity due to cancer treatment is of rising concern, for both cardiologists and oncologists, because it may have a significant impact on cancer patient management and outcome. The most typical manifestation of cardiotoxicity is a hypokinetic cardiomyopathy leading to heart failure. However, the spectrum of the toxic effects that can impair the cardiovascular system may also include acute coronary syndromes, hypertension, arrhythmias, and thromboembolic events. Patients undergoing cancer treatment are more vulnerable to cardiovascular injuries, and their risk of premature cardiovascular disease and death is higher than that of the general population. Prevention of cardiotoxicity remains the most important strategy, and several measures, including cardiac function monitoring, limitation of chemotherapy dose, use of anthracycline analogues and cardioprotectants, and early detection of myocardial cell injury by biomarkers, have been proposed. The response to modern heart failure therapy of cancer treatment-induced cardiomyopathy has never been evaluated in clinical trials, and currently there are no definitive guidelines. Although it is likely that medications used for other forms of cardiomyopathy, particularly angiotensin-converting enzyme inhibitors and ß-blockers, may be highly effective, there is still some unjustified concern regarding their use in cancer patients. Specific guidelines that take cardiologic conditions of cancer patients into account are currently lacking and need to be developed.

[Cardioprotection in women with neoplastic disease]. / La cardioprotezione nelle donne con patologia oncologica.

Cardiotoxicity (CTX) is a serious adverse effect of anticancer drugs that impacts on quality of life and overall survival of cancer patients. Hypokinetic cardiomyopathy is the most typical form of CTX, and it is traditionally considered refractory to therapy. Prevention of CTX remains of paramount importance, and several measures, including serial cardiac function monitoring, reduction of cumulative anthracycline dose, use of anthracycline analogues and cardioprotective agents, have been proposed. Over the last decade, however, a new approach based on cardiac biomarkers has emerged as an effective alternative strategy for the early detection of subclinical cardiac injury. In particular, the role of troponin I in identifying patients at risk of CTX as well as of angiotensin-converting enzyme inhibitors in preventing left ventricular dysfunction and late cardiac events in high-risk patients, namely those with raised troponin I levels after chemotherapy, has been consistently demonstrated as an effective tool for CTX prevention.

Subclinical impairment of coronary flow velocity reserve assessed by transthoracic echocardiography in young renal transplant recipients.

BACKGROUND: In renal transplant recipients (RTR) an increased risk to develop cardiovascular injury is present. Transthoracic Doppler echocardiographic assessment of coronary flow velocity reserve (CFVR), a sensitive and minimally invasive technique, was recently employed to detect both macrovascular and microvascular coronary artery disease (CAD) in different clinical settings. The prevalence of coronary involvement in young adult RTR is still unknown. The aim of the study was to investigate the presence of early cardiovascular damage in asymptomatic young adult RTR. METHODS: Transthoracic Doppler echocardiographic-derived CFVR and common carotid intima-media thickness (IMT) were assessed in 25 asymptomatic young adult RTR (mean age 25.7+/-7.0 years; range 17.3-43.9) without CAD and 25 healthy controls. RESULTS: CFVR was lower in young adult RTR compared to controls (2.8+/-0.6 vs. 3.5+/-0.8; P<0.001), meanwhile left ventricular wall motion and common carotid IMT were comparable in both groups. We found a negative correlation between CFVR and age (r=-0.50; P=0.018) and months on dialysis (r=-0.54; P<0.01). CONCLUSIONS: Young adult RTR showed a reduced CFVR reflecting an impaired coronary microcirculation, which is significantly related to the age and duration of dialysis; coronary microvascular damage is detectable in the absence of changes in common carotid IMT. Non-invasive evaluation of CFVR by transthoracic stress echocardiography could be a reliable method for identification of early coronary microvascular involvement in young adult RTR.