Cardiac toxicity of chemotherapy for breast cancer: do angiotensin-converting enzyme inhibitors and beta blockers protect?

Cardiotoxicity is a relatively frequent and potentially serious side effect of anticancer treatments, particularly anthracyclines and trastuzumab, widely used in the treatment of breast cancer. The increase in cancer survivors has generated a growing interest in the prevention of cardiotoxicity. Although early studies suggested an overall benefit on cardiac function with the use of ACE inhibitors (ACEIs) and beta blockers (BBs), more recent randomized trials have demonstrated little or no effect of pharmacological interventions. Even the various meta-analyses conducted in this area have provided weak results in favour of cardioprotective therapies for which the benefit would not always justify the risk of developing side effects. Given the incompleteness of the evidence, there is no clear consensus on which patients should initiate cardioprotective therapy. As recommended in the new guidelines of the European Society of Cardiology, risk stratification before treatment is crucial to identify high-risk patients who would benefit most from the use of cardioprotective therapy. Randomized trials are currently underway to evaluate other therapeutic strategies such as sacubitril/valsartan, and the possibility of using gliflozins in the future cannot be excluded. However, rigorous control and treatment of risk factors remain the primary focus in the management of these patients.

Prevention of chemotherapy-induced left ventricular dysfunction.

Prevention of left ventricular dysfunction predominantly induced by anthracyclines and/or trastuzumab still represents a challenge for cardio-oncology today. Indeed, this complication threatens to limit the significant gain in cancer survival achieved to date. Oncology strategies with cumulative dose limitation, continuous infusion, dexrazoxane, and liposomal formulations have been shown to decrease the risk of anthracycline cardiotoxicity. The preventive use of ace inhibitors, sartans, and/or beta-blockers has not yet provided convincing evidence and the positive effect on left ventricular ejection fraction decline appears poor without a clear clinical relevance. Assessment of the cardiovascular risk profile is a key aspect of the baseline evaluation of any patient scheduled for cancer therapy. Control and/or correction of modifiable cardiovascular risk factors is the first form of primary prevention of cardiotoxicity. It will be necessary to select populations at higher risk of developing cardiac dysfunction, identify patients genetically predisposed to develop cardiotoxicity in order to build the most appropriate strategies to correctly and timely target cardioprotective therapies.

Concepts in cardiac oncology.

Cardiac oncology is a subspecialty of cardiology engaging cardiologists and oncologists alike, in order to provide the best possible oncologic treatment for patients at high cardiovascular risk or developing cardio-toxicity during the course of their treatment, thus avoiding discontinuing it, and aiming at improving survival and quality of life. Early diagnosis and the effectiveness of the newer cancer treatments delivered an increasing number of long-term survivors (presently almost 30 million worldwide), at high risk of developing cardiovascular diseases. This predisposition has been correlated not only to the toxic side effects of the oncologic treatment but also to a real vulnerability to the risk factors in this patients population. For decades, the concept of cardio-toxicity in cardiac oncology has been restricted to ventricular dysfunction, but during the last few years the Food and Drug Administration has approved hundreds of new molecules and cardiac oncology has escalated its complexity. The introduction of new target therapy, proteasome inhibitors, immuno-modulators, and inhibitors of the immunitary checkpoint, magnified the concept of cardio-toxicity to a wider definition of 'cardiovascular toxicity' incorporating arterial hypertension, ischaemia, cardiomyopathy, myocarditis, arrhythmic complications, long QT, and arterial and venous thrombosis. We are still lacking guidelines on the new and varied forms of toxicity, as well as monitoring strategies in the short- and long-term follow-up.

Effect of Cardioembolic Etiology on Intravenous Thrombolysis Efficacy for Acute Ischemic Stroke.

Previous clinical studies suggest that intravenous (IV) recombinant tissue plasminogen activator (rt-PA) benefits stroke patients regardless of the underlying etiology. In this study, we assessed the possible differences in response to IV rt-PA between cardioembolic stroke and other stroke subtypes. A total of 303 consecutive stroke ischemic patients (from January 2005 to April 2014) admitted to our Stroke Unit and treated with IV rt-PA were retrospectively reviewed. All patients were classified in two groups: Cardioembolic (CE) and Non-Cardioembolic (NCE). We analyzed a total of 303 patients. Thirty patients died in the first hours after fibrinolysis and no statistically significant differences were found in two groups (14 CE vs 18 N-CE). We observed a significant differences in clinical outcome in terms of symptoms "improvement" (p< 0.01 .2) and symptoms" regression" (p<0.057 .2) even if this last result did not reach statistical significance in CE patients respect to N-CE patients. In conclusion, the intravenous fibrinolysis is more effective in CE group than in N-CE regarding symptoms "improvement" and the PFO-Stroke patients treated with fibrinolysis have better outcome than other patients and they have high rate of symptoms" regression". Moreover the main predictor of good outcomes were younger age and milder stroke severity on hospital admission.

Tomographic left ventricular volumetric emptying analysis by real-time 3-dimensional echocardiography: influence of left ventricular dysfunction with and without electrical dyssynchrony.

BACKGROUND: The sequence of left ventricular (LV) systolic emptying is not completely understood. Using real-time 3-dimensional echocardiography, we investigated this sequence and LV synchronicity in physiological and pathological conditions. METHODS AND RESULTS: The study population consisted of 116 healthy volunteers, 20 top-level athletes, 35 patients with LV dysfunction, and 84 patients with LV dysfunction and left bundle-branch block (LBBB). We subdivided the LV into 16 volumetric segments for regional analysis and into apical, middle, and basal regions to calculate the mean of end-systolic times and the time to minimum systolic volume of each region. In healthy volunteers and in top-level athletes, the emptying systolic times increased smoothly from apex to base. These differences determined an apex-to-base time gradient in the LV emptying sequence. In patients with LV dysfunction and without LBBB, this gradient was maintained with a relatively higher LV dyssynchrony. However, in patients with LV dysfunction and LBBB, there was no clear sequence in LV emptying volumes, and this group had the highest LV dyssynchrony. CONCLUSIONS: Real-time 3-dimensional echocardiography tomographic slicing of the LV enables accurate analysis of LV emptying in physiological conditions and in conditions of LV dysfunction with and without electrical dyssynchrony. Progressive dilation of LV produces deterioration in LV synchronicity. However, it is the presence of LV dysfunction in combination with LBBB that determines the loss of the apex-to-base time gradient in LV emptying.

Left ventricular remodelling index (LVRI) in various pathophysiological conditions: a real-time three-dimensional echocardiographic study.

BACKGROUND: Various studies have reported a close correlation between real-time three-dimensional echocardiography (RT3DE) and cine magnetic resonance imaging studies for the assessment of cardiac volumes and mass. OBJECTIVE: The aim of our study was to evaluate changes in left ventricular volumes and mass in subjects with different pathophysiological conditions. A ratio between left ventricular mass and end-diastolic volume (LVRI), detected by RT3DE, was used to describe various patterns of left ventricular remodelling. METHODS: RT3DE was performed to calculate left ventricular end-diastolic (LVEDV) and end-systolic volume (LVESV), ejection fraction (LVEF) and mass in 220 selected subjects. Of these, 152 were healthy volunteers, 19 top-level rowers, 23 patients with dilated cardiomyopathy and 26 patients with hypertrophic cardiomyopathy. Off-line analysis was performed by two independent operators by tracing manual endocardial and epicardial borders of the left ventricle through eight cutting planes. Inter- and intra-observer variability were calculated. RESULTS: Despite the increase in LV volume and mass in the rowers, LVRI remained unchanged compared with control subjects (p = 0.455), while significantly lower values were found patients with dilated cardiomyopathy (p<0.001) and significantly higher values in patients with hypertrophic cardiomyopathy (p<0.001). There was inter- and intra-observer variability. CONCLUSION: The LVRI may serve as a simple and useful indicator of left ventricular adaptation to physiological and pathological conditions.

Frequency and clinical correlates of changes in Thrombolysis In Myocardial Infarction risk score during observation period at emergency department in "low-risk" patients with acute chest pain.

Among 4,333 patients who were triaged in the emergency department (ED) over a 1-year period in 2003 because of acute chest pain, 1,747 (40%) were stratified as "low risk" on the basis of a Thrombolysis In Myocardial Infarction (TIMI) risk score of 0 to 2. Results showed that, during ED stay, TIMI risk score increased to > or =3 in 63% of patients and that such patients were more likely to be diabetic, hypertensive, hyperlipidemic, and smokers, and to have had previous myocardial infarction or revascularization. Patients with changes in TIMI risk score were admitted more often to the hospital, whereas more patients with unchanged TIMI risk score were discharged home directly from the ED. In conclusion, TIMI risk score may change soon after arrival to the ED in 50% of patients with acute chest pain who are initially triaged as low risk. Changes in TIMI risk score are more common in patients with multiple risk factors and/or previous diagnosis of coronary artery disease. Serial, frequent assessments of TIMI score during the ED observation period are mandatory, particularly in these subsets of patients.

Comparison of presenting features, diagnostic tools, hospital outcomes, and quality of care indicators in older (>65 years) to younger, men to women, and diabetics to nondiabetics with acute chest pain triaged in the emergency department.

In a total of 4,843 consecutive patients admitted to an emergency department (ED) with acute chest pain over a 1-year period, presenting features, diagnostic tools, hospital outcomes, and quality-of-care indicators were compared between older (n = 1,781) and younger (n = 3,062) patients, men (n = 3,095) and women (n = 1,748), and diabetics (n = 856) and nondiabetics (n = 3,987). The results showed that after critical pathway implementation, there was an increase in the use of evidence-based treatment strategies in the ED and improved outcomes in older patients, women, and diabetics, with no more differences in the length of ED stay, diagnostic accuracy for myocardial infarction in the ED, door-to-thrombolysis time, and door-to-balloon time compared with younger patients, men, and nondiabetics.

Identification of professional scuba divers with patent foramen ovale at risk for decompression illness.

Functional and anatomic characteristics of patent foramen ovale (PFO) were investigated in 66 professional scuba divers (41 with and 25 without decompression illness) using transthoracic and transesophageal echocardiography. PFO with right-to-left shunting at rest is associated with decompression illness, particularly the neurologic type. A wider patency diameter together with a higher membrane mobility are associated with the risk of developing the disease in divers with PFO.

Critical pathways in the emergency department improve treatment modalities for patients with ST-elevation myocardial infarction in a European hospital.

BACKGROUND: The use of protocols for patients with ST-elevation myocardial infarction (MI) is growing, but no definite conclusion regarding the value of critical pathways in Europe has been drawn. HYPOTHESIS: The aim of this study was to investigate the impact of critical pathway on processes of care and outcome for patients presenting to the emergency department (ED) of a large urban European hospital because of possible ST-elevation MI. METHODS: Critical pathways for management of acute chest pain at our ED were developed in 1998 and have been revised every year. Accordingly, the records of all patients referred in 1997 to the ED because of chest pain (before pathway implementation) and in 2001 (after last pathway revision) were reviewed. An ST-elevation MI was diagnosed at ED in 520 of 5,066 (10.3%) patients with chest pain in 1997, and in 452 of 4,843 (9.3%) patients with chest pain in 2001. Patients were managed according to the ED cardiologists' decisions in 1997, whereas they entered the pathways for ST-elevation MI in 2001, with predefined criteria for diagnosis, thrombolysis, percutaneous coronary intervention, and admission to the coronary care unit. RESULTS: Comparison of treatment modalities disclosed that more patients were given thrombolysis in 1997 (49 vs. 16%, p<0.05), whereas in 2001 more patients were sent to primary angioplasty (63 vs. 11%, p<0.05). Also in 2001, patients more often received aspirin (90 vs. 61%, p<0.05) and intravenous beta blockers (60 vs. 35%, p<0.05) soon after arrival at the ED. Comparison between 1997 and 2001 revealed that admission rates to the coronary care unit (69 vs. 78%, NS) and cardiac wards were similar (19 vs. 10%, NS). Conversely, compared with 1997, patients hospitalized in 2001 had a shorter length of stay (12 +/- 5 vs. 18 +/- 6 days, p<0.05), as well as fewer major adverse coronary events (21 vs. 30%, p<0.05) and lower all-cause in-hospital mortality (12 vs. 20%, p<0.05). The quality of care indicators improved with time, as door-to-electrocardiogram interval (10 +/- 6 vs. 19 +/- 9 min, p<0.05), door-to-needle time (25 +/- 10 vs. 35 +/- 10 min, p<0.05), and door-to-balloon interval (70 +/- 15 vs. 99 +/- 20 min, p<0.05) were shorter in 2001 than in 1997. CONCLUSIONS: A critical pathway for ST-elevation MI at the ED increases the use of evidence-based treatment strategies and improves outcome and quality of care of patients presenting to a European hospital because of acute chest pain.

Qualitative and quantitative evaluation of mitral valve morphology by intraoperative volume-rendered three-dimensional echocardiography.

BACKGROUND AND AIM OF THE STUDY: Two-dimensional echocardiography (2DE) performed to evaluate mitral valve anatomy during valve repair has certain limitations and pitfalls. The study aim was to assess the feasibility, accuracy and incremental value of three-dimensional echocardiography (3DE), coupled with 2DE in evaluating mitral valve structure, before and after repair and pericardial posterior annuloplasty. METHODS: The site and extent of mitral valve prolapse, systolic and diastolic changes of mitral annular area were evaluated using 2D and 3D transesophageal echocardiography (TEE), both pre- and postoperatively in 34 patients before and after mitral valve repair and pericardial posterior annuloplasty. RESULTS: Concordance between 2DE and surgery in evaluating prolapsing mitral valve scallops was 76% for the anterior leaflet and 75% for the posterior leaflet; for 3DE and surgery, concordance was 87% and 93% respectively. There was a significant reduction in maximal and minimal annular area after surgery, with a statistically significant difference between systolic-diastolic changes. CONCLUSION: 3DE, coupled with 2DE, is feasible and accurate in delineating the extent and location of prolapsing scallops of the mitral valve. The combined approach is also valuable in planning mitral valve surgery and evaluating the mitral valve annulus in vivo.