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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the last 10 years the epidemiology of cancer has changed dramatically in Portugal&#44; forcing the National Health System to revise its incidence predictions upward&#46; In 2020 more than 55 000 new cases were identified and more than 65 000 are expected in 2035&#46; All types of cancer are increasing&#44; not only because of longer life expectancy&#44; but also because of modern lifestyles and unhealthy habits&#46; Since breast cancer is the second leading type of cancer and lymphoma is the ninth&#44; and both types are treated effectively with anthracyclines&#44; an increasing incidence of heart failure secondary to chemotherapy is to be expected in the near future&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> This&#44; on top of the already high incidence of heart failure from other causes&#44; is an issue of great concern in daily practice and in the management of the National Health System resources&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In view of this problem&#44; any attempt to reduce the incidence of chemotherapy-related cardiotoxicity with high cost-effectiveness is more than welcome&#46; Unfortunately the evidence regarding cardio-oncology itself is scarce&#59; most studies are observational and randomized trials have a small number of participants &#40;in no case more than a few hundred&#41;&#44; while randomized trials in oncology that have large study populations they report few cardiovascular side effects&#44; which does not fit with real-world practice&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In their study published in this issue of the <span class="elsevierStyleItalic">Journal</span>&#44; considering these two issues &#8211; the need to reduce the burden of heart failure&#44; and the lack of solid evidence in cardio-oncology &#8211; Sampayo et al&#46; tested two heart failure treatment approaches&#44; in order to determine which is more cost-effective&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> The conventional approach was extrapolated from the European Society of Cardiology cardiotoxicity guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> in which treatment with a beta-blocker and an angiotensin-converting enzyme inhibitor &#40;ACEi&#41; was started only after a diagnosis of heart failure&#44; defined as an asymptomatic decline in left ventricular ejection fraction &#40;LVEF&#41; of &#8805;10&#37; to a final value &#8804;55&#37;&#46; The second approach&#44; universal cardioprotection &#40;UCP&#41;&#44; was derived from the OVERCOME trial&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> in which patients were randomized to enalapril and carvedilol &#40;intervention arm&#41; or no intervention &#40;control arm&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Sampayo at al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> used data from their own center to calculate the costs and quality-adjusted life-years &#40;QALYs&#41; of imaging-guided surveillance &#40;cardioprotective drugs prescribed according to LVEF&#41; or UCP &#40;beta-blocker and ACEi for all patients&#41;&#46; To obtain the QALYS and costs&#44; they used a Monte Carlo simulation of a Markov model&#44; the main characteristic of which is that although individual patients are subject to the same transition probabilities&#44; they may or may not move between the stages of each cycle&#46; Thus&#44; the path followed by different patients will vary&#44; due to random variability&#46; In a Monte Carlo simulation&#44; values are sampled at random from the input probability distributions&#46; This process is computed hundreds or thousands of times&#44; and the result is a probability distribution of possible outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> The microsimulation in the present study modeled a hypothetical cohort of 1000 patients over a five-year horizon&#46; Although other base cases were tested&#44; the major findings are obviously those of the reference case corresponding to a 63-year-old woman with breast cancer treated sequentially with anthracyclines and trastuzumab&#44; for whom the LVEF-guided strategy &#40;4&#46;22 QALYs&#44; &#8364;2594 over five years&#41; was superior to the UCP strategy &#40;3&#46;42 QALYs&#44; &#8364;3758 over five years&#41;&#46; Although Markov models&#44; like all statistical analyses&#44; have their limitations&#44; it is difficult to refute these findings&#44; not only because patients are dissimilar in their genetic background&#44; but also because the extent of the disease and comorbidities are different&#46; This is why precision medicine is becoming so popular&#58; one size does not fit all&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">And why is precision medicine so desirable&#63; First&#44; depending on the series&#44; cardiotoxicity occurs in 3-20&#37; of cancer cases&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> so even in the worst scenario only one fifth of patients will have reduced LVEF&#59; and second&#44; management of neurohormonal blockade in cancer patients is generally more challenging than in the other major heart failure etiologies&#44; especially because of hypotension resulting from vomiting&#44; weight loss and co-medication&#46; A UCP strategy is intuitively the worse option in these patients&#46; Intuition apart&#44; we should always be guided by evidence&#44; and the most robust supports the treatment of reduced LVEF recommended in the guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> which is based on clinical trials with thousands of patients&#44; from CONSENSUS in 1986 to the latest trials with sacubitril&#47;valsartan and sodium&#47;glucose cotransporter 2 inhibitors&#46; These trials included many more participants than the two major studies of UCP in cancer patients&#44; OVERCOME &#40;90 patients&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> and PRADA &#40;130 patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Interestingly&#44; oncologists &#8211; like most physicians &#8211; believe strongly that cancer treatment should be started immediately after diagnosis&#44; but unfortunately cardiologists are not aware that it is urgent not only to start heart failure treatment&#44; but also to titrate it&#46; This is why a personalized approach is so important in cancer patients with heart failure&#46; The chosen therapeutics should be adjusted to the individual clinical presentation and comorbidities and should also be rapidly titrated &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless&#44; cardio-oncology is definitely on the right track&#44; as cardiovascular mortality in cancer patients has decreased significantly in recent years&#44; as shown by the CARDIOTOX registry &#40;0&#46;4&#37; cardiovascular mortality&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> much less than previous reports &#40;16&#37; 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One size does not fit all: Also true for cardio-oncology
Um tamanho não serve a todos - também verdade na cardio-oncologia
Lígia Mendes
Hospital da Luz Setúbal, Setúbal, Portugal
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Different titration algorithms according to the clinical condition of cancer patients with heart failure&#46; ACEi&#58; angiotensin-converting enzyme inhibitor&#59; ARNi&#58; angiotensin receptor neprilysin inhibitor&#59; LVEF&#58; left ventricular ejection fraction&#59; MRA&#58; mineralocorticoid receptor antagonist&#59; SGLT2i&#58; sodium-glucose cotransporter-2 inhibitor&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">In the last 10 years the epidemiology of cancer has changed dramatically in Portugal&#44; forcing the National Health System to revise its incidence predictions upward&#46; In 2020 more than 55 000 new cases were identified and more than 65 000 are expected in 2035&#46; All types of cancer are increasing&#44; not only because of longer life expectancy&#44; but also because of modern lifestyles and unhealthy habits&#46; Since breast cancer is the second leading type of cancer and lymphoma is the ninth&#44; and both types are treated effectively with anthracyclines&#44; an increasing incidence of heart failure secondary to chemotherapy is to be expected in the near future&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">1</span></a> This&#44; on top of the already high incidence of heart failure from other causes&#44; is an issue of great concern in daily practice and in the management of the National Health System resources&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In view of this problem&#44; any attempt to reduce the incidence of chemotherapy-related cardiotoxicity with high cost-effectiveness is more than welcome&#46; Unfortunately the evidence regarding cardio-oncology itself is scarce&#59; most studies are observational and randomized trials have a small number of participants &#40;in no case more than a few hundred&#41;&#44; while randomized trials in oncology that have large study populations they report few cardiovascular side effects&#44; which does not fit with real-world practice&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In their study published in this issue of the <span class="elsevierStyleItalic">Journal</span>&#44; considering these two issues &#8211; the need to reduce the burden of heart failure&#44; and the lack of solid evidence in cardio-oncology &#8211; Sampayo et al&#46; tested two heart failure treatment approaches&#44; in order to determine which is more cost-effective&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> The conventional approach was extrapolated from the European Society of Cardiology cardiotoxicity guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> in which treatment with a beta-blocker and an angiotensin-converting enzyme inhibitor &#40;ACEi&#41; was started only after a diagnosis of heart failure&#44; defined as an asymptomatic decline in left ventricular ejection fraction &#40;LVEF&#41; of &#8805;10&#37; to a final value &#8804;55&#37;&#46; The second approach&#44; universal cardioprotection &#40;UCP&#41;&#44; was derived from the OVERCOME trial&#44;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> in which patients were randomized to enalapril and carvedilol &#40;intervention arm&#41; or no intervention &#40;control arm&#41;&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Sampayo at al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">4</span></a> used data from their own center to calculate the costs and quality-adjusted life-years &#40;QALYs&#41; of imaging-guided surveillance &#40;cardioprotective drugs prescribed according to LVEF&#41; or UCP &#40;beta-blocker and ACEi for all patients&#41;&#46; To obtain the QALYS and costs&#44; they used a Monte Carlo simulation of a Markov model&#44; the main characteristic of which is that although individual patients are subject to the same transition probabilities&#44; they may or may not move between the stages of each cycle&#46; Thus&#44; the path followed by different patients will vary&#44; due to random variability&#46; In a Monte Carlo simulation&#44; values are sampled at random from the input probability distributions&#46; This process is computed hundreds or thousands of times&#44; and the result is a probability distribution of possible outcomes&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">7</span></a> The microsimulation in the present study modeled a hypothetical cohort of 1000 patients over a five-year horizon&#46; Although other base cases were tested&#44; the major findings are obviously those of the reference case corresponding to a 63-year-old woman with breast cancer treated sequentially with anthracyclines and trastuzumab&#44; for whom the LVEF-guided strategy &#40;4&#46;22 QALYs&#44; &#8364;2594 over five years&#41; was superior to the UCP strategy &#40;3&#46;42 QALYs&#44; &#8364;3758 over five years&#41;&#46; Although Markov models&#44; like all statistical analyses&#44; have their limitations&#44; it is difficult to refute these findings&#44; not only because patients are dissimilar in their genetic background&#44; but also because the extent of the disease and comorbidities are different&#46; This is why precision medicine is becoming so popular&#58; one size does not fit all&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">And why is precision medicine so desirable&#63; First&#44; depending on the series&#44; cardiotoxicity occurs in 3-20&#37; of cancer cases&#44;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">8</span></a> so even in the worst scenario only one fifth of patients will have reduced LVEF&#59; and second&#44; management of neurohormonal blockade in cancer patients is generally more challenging than in the other major heart failure etiologies&#44; especially because of hypotension resulting from vomiting&#44; weight loss and co-medication&#46; A UCP strategy is intuitively the worse option in these patients&#46; Intuition apart&#44; we should always be guided by evidence&#44; and the most robust supports the treatment of reduced LVEF recommended in the guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> which is based on clinical trials with thousands of patients&#44; from CONSENSUS in 1986 to the latest trials with sacubitril&#47;valsartan and sodium&#47;glucose cotransporter 2 inhibitors&#46; These trials included many more participants than the two major studies of UCP in cancer patients&#44; OVERCOME &#40;90 patients&#41;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">6</span></a> and PRADA &#40;130 patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Interestingly&#44; oncologists &#8211; like most physicians &#8211; believe strongly that cancer treatment should be started immediately after diagnosis&#44; but unfortunately cardiologists are not aware that it is urgent not only to start heart failure treatment&#44; but also to titrate it&#46; This is why a personalized approach is so important in cancer patients with heart failure&#46; The chosen therapeutics should be adjusted to the individual clinical presentation and comorbidities and should also be rapidly titrated &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0035" class="elsevierStylePara elsevierViewall">Nevertheless&#44; cardio-oncology is definitely on the right track&#44; as cardiovascular mortality in cancer patients has decreased significantly in recent years&#44; as shown by the CARDIOTOX registry &#40;0&#46;4&#37; cardiovascular mortality&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">10</span></a> much less than previous reports &#40;16&#37; cardiovascular mortality in breast cancer patients&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">11</span></a> The CARDIOTOX prospective registry included 865 patients and used LVEF to define cardiotoxicity&#46; Myocardial dysfunction was identified in 37&#46;5&#37; of patients during follow-up &#40;95&#37; confidence interval 34&#46;22-40&#46;8&#37;&#41;&#44; 31&#46;6&#37; with mild&#44; 2&#46;8&#37; with moderate&#44; and 3&#46;1&#37; with severe myocardial damage&#47;dysfunction&#46; Despite the high incidence of cardiotoxicity&#44; cardiovascular mortality was only 0&#46;4&#37;&#46; It is our belief that these results are representative of contemporary cardio-oncology clinics&#44; which follow the recommendations of the current ESC heart failure<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">5</span></a> and European Society for Medical Oncology guidelines&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">12</span></a> treating patients only after an imaging diagnosis of myocardial dysfunction with an individualized drug approach&#46;</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0040" class="elsevierStylePara elsevierViewall">The author has no conflicts of interest to declare&#46;</p></span></span>"
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ISSN: 21742049
Original language: English
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Revista Portuguesa de Cardiologia (English edition)