Oncology and Cardiac Rehabilitation: An Underrated Relationship.

Cancer and cardiovascular diseases are globally the leading causes of mortality and morbidity. These conditions are closely related, beyond that of sharing many risk factors. The term bidirectional relationship indicates that cardiovascular diseases increase the likelihood of getting cancer and vice versa. The biological and biochemical pathways underlying this close relationship will be analyzed. In this new overlapping scenario, physical activity and exercise are proven protective behaviors against both cardiovascular diseases and cancer. Many observational studies link an increase in physical activity to a reduction in either the development or progression of cancer, as well as to a reduction in risk in cardiovascular diseases, a non-negligible cause of death for long-term cancer survivors. Exercise is an effective tool for improving cardio-respiratory fitness, quality of life, psychological wellbeing, reducing fatigue, anxiety and depression. Finally, it can counteract the toxic effects of cancer therapy. The protection obtained from physical activity and exercise will be discussed in the various stages of the cancer continuum, from diagnosis, to adjuvant therapy, and from the metastatic phase to long-term effects. Particular attention will be paid to the shelter against chemotherapy, radiotherapy, cardiovascular risk factors or new onset cardiovascular diseases. Cardio-Oncology Rehabilitation is an exercise-based multi-component intervention, starting from the model of Cardiac Rehabilitation, with few modifications, to improve care and the prognosis of a patient's cancer. The network of professionals dedicated to Cardiac Rehabilitation is a ready-to-use resource, for implementing Cardio-Oncology Rehabilitation.

Usefulness of N-terminal pro-B-type natriuretic peptide levels in predicting residual myocardial ischemia in patients with ST elevation acute myocardial infarction.

AIM: N-terminal pro-b-type natriuretic peptide (NT pro-BNP) is a neurohormone synthesized predominantly in ventricular myocardium. In patients with symptoms of heart failure, elevation in NT pro-BNP accurately identifies ventricular dysfunction. However, NT pro-BNP levels are not specific for ventricular dysfunction in patients who do not have overt symptoms of heart failure, suggesting that other cardiac processes such as myocardial ischemia may also cause elevation in NT pro-BNP. The study was aimed to determine whether NT pro-BNP elevations are associated with myocardial ischemia. METHODS: One hundred and thirty patients (104 males, 26 females, mean age 61+12 years), with ST elevation acute myocardial infarction (STEMI) and preserved left ventricular ejection fraction (>45%) at echocardiography performed at entry, from February 2003 and February 2004 were enrolled. In all patients NT pro-BNP plasma levels were checked at entry and 4-5 days after symptoms onset. In addition, maximal or symptom-limited exercise treadmill test (Bruce protocol), and myocardial perfusion scintigraphy using [(99m)Tc]Tetrofosmin single photon emission computed tomography (SPECT) imaging were performed within 30 days of STEMI. Ischemia was defined as reversible perfusion abnormalities. RESULTS: Of the 130 participants, 66 (51%) had inducible ischemia. Compared with patients in the lowest tertile, those in the highest tertile of NT pro-BNP had a greater significant risk of residual ischemia (odds ratio: 8.66; 95% CI, 3.90 to 19.24). Nevertheless patients in the highest tertile were older (64.19+/-10.80 years versus 55.90+/-9.67 years, P = 0.0001), had a lower left ventricular ejection fraction (49.70+13.46% versus 59.49+/-6.58%, P = 0.0001) and had a great rate of acute myocardial infarction (anterior acute myocardial infarction = 40.63% versus 25%). CONCLUSIONS: Elevated levels of NT pro-BNP are associated with residual myocardial ischemia among patients with STEMI and preserved left ventricular ejection fraction, as demonstrated by perfusion defect on SPECT imaging, suggesting that these patients may need further evaluation for stratification of the future risk of fatal events. The observed association between NT pro-BNP levels and ischemia may explain because tests for NT pro-BNP are not specific for ventricular dysfunction among patients with coronary artery disease.

Increased reperfusion by glycoprotein IIb/IIIa receptor antagonist administration in case of unsuccessful and failed thrombolysis in patients with acute myocardial infarction: a pilot study.

BACKGROUND: The aim of this study was to evaluate the effectiveness of glycoprotein (GP) IIb/IIIa receptor inhibitors in acute myocardial infarction (AMI) patients in case of unsuccessful and failed thrombolysis. METHODS: Eighty-four patients hospitalized within 4 hours of symptom onset were randomized (single blind) into two groups. Regardless of the group, placebo or GP IIb/IIIa inhibitors were administered to patients who did not present with reperfusion signs (failed thrombolysis) 30 min after starting thrombolysis and 30-60 min after the end of full thrombolysis in patients with pain recurrence and ST-segment elevation (unsuccessful thrombolysis). Reperfusion was assessed by the creatine kinase peak occurring within 12 hours, by the observation of rapid ST-segment reduction (50-70% within 1 hour) in the 12-lead ECG continuous tracing, by the rapid regression of pain and by the development of early ventricular arrhythmias. Group 1 patients (n = 42) received, during failed thrombolysis or after 30-60 min of effective thrombolysis but with pain recurrence and ST-segment elevation (unsuccessful thrombolysis), treatment with i.v. GP IIb/IIIa inhibitors, heparin according to the TIMI 14 trial, and aspirin. Group 2 patients (n = 42) received a full dose of recombinant tissue-type plasminogen activator (rt-PA 100 mg) and placebo either during failed thrombolysis or, after 30 min of effective thrombolysis but with pain recurrence and ST-segment elevation, and standard heparin treatment and aspirin. RESULTS: In group 1, 39 patients showed rapid reperfusion (4 +/- 3 min); 22 patients received rt-PA 65 mg and 20 patients received rt-PA 100 mg and subsequent GP IIb/IIIa inhibitor treatment. Coronary angiography, performed after 12-72 hours showed patency of the infarct-related artery in 39 patients whose clinical picture was suggestive of rapid reperfusion during administration of a bolus of GP IIb/IIIa inhibitors. In group 2, no patients showed reperfusion and they were submitted to rescue coronary angioplasty (p < 0.05). Side effects occurred in 3 cases in group 1 and in 2 cases in group 2. Patients receiving GP IIb/IIIa inhibitors showed a reduced incidence of stent treatment (p = NS) and a significant reduction in the occurrence of events (angina) within 30 days of treatment (p = NS). CONCLUSIONS: Our data suggest that in patients with AMI and failed thrombolysis, treatment with GP IIb/IIIa receptor inhibitors is feasible. The increase in the risk of bleeding was acceptable. The most important result was that this combination is safe.

Safety and efficacy of thrombolysis with alteplase (50 mg) plus tirofiban versus alteplase (100 mg) alone in acute myocardial infarction: preliminary findings.

BACKGROUND: The goal of therapy in acute myocardial infarction (AMI) is the complete and timely restoration of coronary blood flow. Platelets have a pivotal role in the pathophysiology of AMI. The study was aimed at evaluating the safety and efficacy of the combination of 50 mg alteplase plus tirofiban vs 100 mg alteplase in AMI patients. METHODS: One hundred twenty patients (83 males, 37 females; mean age 54.3 +/- 8 years) were hospitalized for suspected AMI within 6 hours of the onset of symptoms. All patients presented pain and persistent ST-segment elevation, were suitable candidates for thrombolysis (1st episode) and were randomized (double blind) into two groups. Group A (n = 60,42 males, 18 females) received 50 mg alteplase (15 mg as bolus, followed by an infusion of 35 mg over 60 min) in combination with tirofiban (0.4 mcg/kg/min for 30 min followed by an infusion of 0.1 mcg/kg/min for 3 days). Group B (n = 60, 41 males, 19 females) received 100 mg of accelerated-dose alteplase alone. Reperfusion criteria were defined as follows: > 50% reduction in the ST-segment elevation; resolution of chest pain; double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis; reperfusion arrhythmias within the first 120 min of thrombolysis. The blood pressure, heart rate and ECG were continuously monitored. The mortality, re-AMI, recurrent angina, major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: The groups were similar with regard to clinical data, risk factors, time elapsed from the onset of symptoms to thrombolytic therapy and AMI localization. Forty-seven patients (78.3%) from group A showed reperfusion (15-60 min) vs 25 patients (41.7%) from group B (43-105 min after the end of full-thrombolysis, p = 0.01). Group A patients showed an earlier CK peak and lower CK and CK-MB peaks than those in the control group (p = 0.0001, p = 0.011, p = 0.005, respectively). Nine patients (7.5%) died: 6 (10%) in group B and 3 (5%) in group A (p = NS). A non-fatal re-AMI occurred in 8 patients from group A and in 4 patients from group B (p = NS). Recurrent angina occurred in 27 patients (45%) from group A and in 11 (18.3%) from group B (p = 0.037). Twenty-three of these patients underwent urgent coronary angioplasty (17 from group A and 6 from group B) and 3 from group A and 1 from group B underwent urgent coronary artery bypass grafting (p = NS). The frequency of minor bleeding was higher in group A than in group B (56.7 vs 25%, p = 0.033). No major bleeding was observed in the study groups. At the predischarge echocardiogram, the ejection fraction was higher in group A than in group B (50 +/- 9 vs 44 +/- 7%, p = 0.001). CONCLUSIONS: Our data suggest that the combination of glycoprotein IIb/IIIa inhibitors plus alteplase is feasible in AMI patients and that the increased risk of bleeding is an acceptable risk considering the advantage in terms of the reduction in the extent of an AMI. In addition, this combination can allow one to gain time when it is necessary to perform mechanical revascularization in patients admitted to a hospital without an interventional cardiology laboratory or in those who have to be referred to another hospital for urgent coronary artery bypass grafting.

Additional beneficial effects of canrenoate in patients with anterior myocardial infarction on ACE-inhibitor treatment. A pilot study.

BACKGROUND: Recent evidence suggests that, via the mineralocorticoid receptors present in cardiovascular tissues, aldosterone exerts profibrotic effects, and that partial aldosterone escape occurs during ACE-inhibitor treatment. METHODS: A double-blind, randomized study was performed in order to evaluate the feasibility, tolerability, and the effects of the administration of 25 mg/day of canrenoate plus captopril versus captopril alone to patients with anterior acute myocardial infarction (AMI) unsuitable for or not receiving thrombolytic treatment and to patients in whom such treatment resulted or did not result in reperfusion. One hundred eighty-seven patients with anterior AMI were included in the present study. In all cases serum creatinine concentrations and serum K concentrations were < 2.0 mg/dl and < 5.5 mmol/l respectively. The patients were randomized in two groups: the canrenoate group included 94 patients who received captopril and 25 mg i.v. of canrenoate (1 mg/hour for the first 72 hours and then orally 25 mg/day) whereas the placebo group (93 patients) received captopril and placebo. On admission and on days 10, 90 and 180 all patients underwent echocardiography in order to determine the end-systolic volume (ESV), the ejection fraction (EF), the end-diastolic diameter, the E/A ratio, the E deceleration time as well as the isovolumetric relaxation time (IVRT) and the E and A peak velocities. RESULTS: Unreperfused patients did not show patency of the infarct-related artery whereas in reperfused patients this vessel was patent (7-10 days after AMI). The two groups were similar in age, sex, incidence of diabetes, smoking habits, hypertension, creatine kinase enzymatic peak, adjuvant therapy, baseline EF, ESV, and incidence of coronary artery bypass grafting/coronary angioplasty. Following 10 days of treatment (canrenoate group), only 9 patients presented with serum K and creatinine concentrations respectively > 5.5 mmol/l and > 2.0 mg/dl. Among those patients receiving canrenoate, the mitral E/A ratio was higher compared to the placebo group (p = 0.001) whereas the ESV was significantly reduced (p < 0.05). The deceleration time for reperfused patients receiving canrenoate was higher than that observed for reperfused patients in the placebo group. The intragroup EF was significantly increased (p = 0.042). Compared to the placebo group, the IVRT was significantly higher for unreperfused patients receiving canrenoate than in the placebo group (p = 0.001). Serum creatinine, blood urea and K levels as well as the incidence and extent of vessel disease were similar for both groups. No side effects were observed during the study period. CONCLUSIONS: Our data suggest that the combination of captopril plus canrenoate is feasible for the initial treatment of patients presenting with AMI. Besides, compared to captopril alone it is more efficacious in improving the E/A ratio, the ESV, the EF, and the IVRT.

Utility and safety of immediate exercise testing of low-risk patients admitted to the hospital with acute chest pain.

It is common practice to hospitalize patients with chest pain for a period of observation and to perform further diagnostic evaluation such as exercise treadmill testing (ETT) once acute myocardial infarction (AMI) has been excluded. This study evaluates the safety and efficacy of immediate ETT for patients admitted to the hospital with acute chest pain. One hundred and ninety non-consecutive low-risk patients admitted to the hospital from emergency department with acute chest pain underwent ETT using Bruce protocol immediately on admission to the hospital (median time 165+30 min). Fifty-seven (30%) patients had positive exercise electrocardiograms, 44 (77.2%) of whom had significant coronary narrowing by angiography. An uncomplicated anterior non-Q-wave AMI was diagnosed in one patient. One hundred and eleven (58.4%) patients had negative and 22 (11.6%) patients had non-diagnostic exercise electrocardiograms. Of these 133 patients, 86 (64.7%) were discharged immediately after ETT, 19 (14.3%) were discharged within 24 h, and 28 (21%) were discharged after 24 h of observation. There were no complications from ETT. During the 17+/-6 months follow-up no patients died, and only eight (7.2%) patients with negative ETT experienced a major cardiac event (one AMI and seven angina). In conclusion, our results suggest that immediate ETT of low-risk patients with chest pain who are at sufficient risk to be designated for hospital admission, is effective in further stratifying this group into those who can be safety discharged immediately and those who require hospitalization.

[The safety and efficacy of systemic salvage thrombolysis in acute myocardial infarct]. / Sicurezza ed efficacia della trombolisi di salvataggio per via sistemica nell'infarto miocardico acuto.

BACKGROUND: Thrombolysis reduces mortality in patients with acute myocardial infarction hospitalized within 6 hours of the symptom onset. Infarctions involving a small area of the myocardium show a lower mortality in comparison to those involving a large area. The aim of this study was to evaluate the safety and efficacy of rescue thrombolysis in patients with large acute myocardial infarction who had failed standard thrombolysis. METHODS: From January 1995 to December 1997, ninety patients (69 males, 21 females, mean age 56.7 +/- 9 years), hospitalized for suspected acute myocardial infarction within 4 hours of the symptom onset, suitable for thrombolysis (first episode), and who experienced pain and showed persistent ST segment elevation 120 min after starting thrombolysis, were randomized (single blind) into two groups: Group A (n = 45) received an additional thrombolytic treatment (rt-PA 50 mg), 10 mg as a bolus plus 40 mg in 60 min; Group B (n = 45) received conventional therapy. Positive non-invasive markers were defined as follows: resolution of chest pain; > 50% reduction in ST segment elevation; double marker of creatine phosphokinase (CPK) and CK-MB activity 2 hours after the start of thrombolysis; occurrence of reperfusion arrhythmias within the first 120 min of thrombolytic therapy. Blood pressure, heart rate and ECG were continuously monitored. Echocardiogram was carried out at entry and before discharge to control ejection fraction and segmental wall motion. Adverse events such as death, reinfarction, recurrent angina, incidence of major and minor bleeding, and emergency bypass surgery or coronary angioplasty were checked. RESULTS: Thirty-five patients (77.7%) showed reperfusion (10-50 min) after the start of additional rt-PA. In patients who did not receive additional thrombolysis, only 12 (26.6%) showed reperfusion 65-115 min after the end of rt-PA infusion. Group A showed an earlier and lower CK and CK-MB peak than Group B (p = 0.0001, p = 0.009, and p = 0.002, respectively). Mortality (n = 16, 17.7%) was higher in Group B (n = 13) than in Group A (n = 3) (28.8 vs 6.6%, p = 0.041). Seven patients from Group A showed non-fatal reinfarction. Angina was observed in 18 (40%) patients from Group A and 3 (6.6%) from Group B (p = 0.006). Ten of these patients underwent urgent coronary angioplasty (9 from Group A and 1 from Group B) and 3 from Group A urgent bypass surgery. Minor bleeding was higher in Group A than in Group B (44.4 vs 15.5%, p = 0.047). A major bleeding was observed in Group A (non-fatal stroke). At predischarge echocardiogram ejection fraction was higher in Group A than in Group B (46 +/- 8 vs 38 +/- 7%, p = 0.0001). CONCLUSIONS: Our data suggest that an additional dose of a thrombolytic drug in patients with unsuccessful thrombolysis is feasible, and the bleeding increase is an acceptable risk in comparison with the advantages obtained from a reduced infarct extension. Rescue thrombolysis could save time and allow mechanical revascularization to be carried out in patients admitted to a hospital without interventional cardiology laboratory or in those who have to be refereed to other hospitals for urgent bypass surgery.

Efficacy of rescue thrombolysis in patients with acute myocardial infarction: preliminary findings.

Thrombolysis reduces mortality in patients with acute myocardial infarction (AMI) who are hospitalized within 6 hours from the onset of symptoms. AMIs involving a small area of myocardium show a lower mortality in comparison with AMI involving a large area. The present study was aimed at evaluating the safety and efficacy of rescue thrombolysis in patients with large AMI who had failed thrombolysis. Ninety patients (69 Males and 21 Females), mean age 56.7 +/- 9 years, hospitalized for suspected AMI within 4 hours from the onset of symptoms, suitable for thrombolysis (First episode), and showing pain and persistent ST segment elevation 120 minutes after starting thrombolysis, were randomized (double-blind) into two groups. Group A (45 patients: 10 females and 35 males) received an additional thrombolytic treatment (rTPA 50 mg), 10 mg as bolus plus 40 mg in 60 minutes. Group B (45 patients: 11 females and 34 males) received placebo. Positive noninvasive markers were defined as follows: (1) resolution of chest pain, (2) > or = 50% reduction in ST segment elevation, (3) double marker of creatine kinase (CK) and CK-MB activity 2 hours after the start of thrombolysis, and (4) occurrence of reperfusion arrhythmias within the first 120 minutes of thrombolytic therapy. Blood pressure, heart rate, and ECG were continuously monitored. An echocardiogram was carried out at entry, and before discharge, to control ejection fraction and segmentary kinetics. Adverse events such as death, re-AMI, recurrent angina, incidence of major and minor bleeding, and emergency CABG/PTCA were checked. The groups were similar in terms of age, sex, diabetes, smoking habits, hypertension, and adjuvant therapy (beta-blockers). No significant difference was observed between the two groups regarding the time elapsed from the onset of symptoms to thrombolysis and AMI localization. Thirty-five patients (77.7%) showed reperfusion (10-50 minutes) after commencement of additional rTPA. Of the patients receiving placebo, 12 (26.6%) showed reperfusion within 35-85 minutes. Group A showed an earlier and lower CK and CK-MB peak than the control group, (respectively, p = 0.0001-0.009 and 0.002). Mortality (17.7%, 16 patients) was higher in group B than in the additional rTPA group, i.e., 6.6% (3 patients) in group A versus 28.8% (13 patients) in Group B (p = 0.041). Seven patients from group A showed nonfatal re-AMI. Angina was observed in 18 patients (40%) from group A and 3 (6.6%) from group B (p = 0.006). Ten of these patients underwent urgent PTCA (9 from group A and 1 from group B), and 3 from group A underwent urgent CABG. Minor bleeding was higher in group A than in group B (44.4% versus 15.5%, p = 0.047). Major bleeding was observed in group A (nonfatal stroke). At predischarge, the echocardiogram ejection fraction was higher in group A than in group B (46 +/- 8% versus 38 +/- 7%, p = 0.0001). Our data suggest that an additional dose of thrombolytic drug in patients with unsuccessful thrombolysis is feasible and also that the bleeding increase is an acceptable risk in comparison with the advantages obtained in reducing AMI extension. Rescue thrombolysis can allow a gain in time to perform mechanical revascularization in patients admitted to hospital without an interventionist cardiology laboratory or in those who have to be referred to another hospital for urgent CABG.

[Two cases of "scombroid syndrome" with severe cardiovascular compromise]. / Due casi di "sindrome sgombroide" con importante compromissione cardiovascolare.

Two cases of severe intoxication after ingestion of cooked tuna fish were observed. Symptoms and clinical signs were consistent with the scombroid syndrome. Cardiovascular shock was observed in both patients and was associated with subendocardial myocardial infarction in 1 case and acute pulmonary edema with myocardial ischemia in the other. The importance of ECG monitoring in the Intensive Coronary Care Unit is stressed.

[Comparison of the echo-dobutamine-atropine test and ergometric test in the diagnosis of coronary disease]. / Confronto tra test eco-dobutamina-atropina e test ergometrico nella diagnosi di malattia coronarica.

BACKGROUND: A prospective study has been done on 46 patients with suspected coronary artery disease (CAD). They had no history of myocardial infarction (MI) and a normal basal kinetic echocardiography. This was done in order to evaluate the overall accuracy of dobutamine-atropine stress echocardiography (DAS) compare to exercise stress test (ET) for the diagnosis of CAD. METHODS: All the patients after suspension of coronary therapy, performed a casual sequence with both maximal or symptom limited exercise testing (treadmill-Bruce protocol) and DAS. The dobutamine has been given while monitoring systemic blood pressure, electrocardiography and echocardiography in steps of 10 mcg/kg/min' per 3 min' up to a maximum of 40 mcg/kg/min'. Atropine has been added (0.25-1 mg) in patients who did not reach the theoretical maximal cardiac frequency. The test is considered positive when kinetic segmental left ventricular dysfunction appeared. CAD was defined as 50% luminal area stenosis in at least 1 coronary artery at coronary angiography. RESULTS: Significant CAD was present in 27/46 patients (59%). Compared with ET, DAS had significantly higher sensitivity (59% vs 92%, p = 0.01). The different sensibility between the two tests was higher on these patients with a 1 vessel disease (40% vs 86%, p = 0.02). There were no significant differences in specificity among the two tests (79% vs 84%, respectively). Differences in overall accuracy between ET and DAS were significant (67% vs 89%, p = 0.02). CONCLUSIONS: The results of our study show that the DAS is a safe and feasible technique with high sensibility (especially in patients with single CAD) and specificity. This is a valid alternative to the traditional ET, especially for these patients unable to exercise or these who are poorly motivated to achieve a work load sufficient to make the test interpretable.

Value of negative predischarge exercise testing in identifying patients at low risk after acute myocardial infarction treated by systemic thrombolysis.

Although thrombolytic therapy reduces mortality in patients with acute myocardial infarction (AMI), it is associated with a greater incidence of successive coronary events, and there is still no ideal diagnostic and therapeutic strategy for such patients. The present study verifies the value of negative predischarge exercise testing in identifying low-risk patients treated with thrombolysis after AMI. One hundred fifty-seven consecutive patients with an uncomplicated clinical course underwent maximal or symptom-limited exercise testing (Bruce treadmill protocol) within 15 days of AMI in the absence of therapy. The location of the AMI was anterior in 51 patients, inferior in 85 and non-Q-wave in 21. All of the patients were followed for 6 months. Death and nonfatal reinfarction were considered as major coronary events, and the recurrence of angina as a minor event. Exercise test results were negative in 105 patients (group 1) and positive for angina or ST depression greater than or equal to 0.1 mV in 52 (group 2). No deaths occurred during follow-up; there were 3 reinfarctions (3%) and 7 cases (7%) of postinfarction angina in group 1, and 2 reinfarctions (4%) and 21 cases (40%) of postinfarction angina in group 2. By the end of follow-up, 90% of the patients with negative exercise test results were event-free (97% in the case of major events). These results show that thrombolytic therapy does not affect the value of negative postinfarction exercise testing in identifying low-risk patients.