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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We read with great interest the manuscript by J Silva-Cardoso et al&#46; entitled &#8220;SGLT-2 inhibitors&#58; A step forward in the treatment of heart failure with reduced ejection fraction&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> In their article&#44; the authors performed a literature review to analyze how SGLT-2 inhibitors have emerged as the fourth pillar of pharmacological disease-modifying therapy in heart failure with reduced ejection fraction &#40;HFrEF&#41; patients&#44; regardless of the presence or absence of diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> After a close reading of the article&#44; we would like to reflect on the current situation of heart failure with preserved ejection fraction &#40;HFpEF&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The extensive evidence with HFrEF lack in HFpEF up to Emperor trial&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> In patients with stable HF and left ventricle ejection fraction &#62;40&#37;&#44; the Emperor trial showed a 21&#37; reduction in the primary endpoint &#40;composite of cardiovascular death or HF hospitalization&#41; at a median follow-up of 26&#46;2 months&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> This effect was mainly due to a decrease in the risk of hospitalization&#59; indeed&#44; patients on empagliflozin showed a reduction of 27&#37; in the total HF hospitalization that occurred during follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> However&#44; a neutral effect was found for all cause-mortality &#40;hazard ration &#40;HR&#41;&#58; 1&#46;00&#59; 95&#37; confidence interval &#40;CI&#41;&#44; 0&#46;87-1&#46;15&#41; and total rehospitalizations &#40;HR&#58; 0&#46;93&#59; 95&#37; CI&#44; 0&#46;85-1&#46;01&#41;&#46; Interestingly&#44; non-HF hospitalizations and non-CV-death accounted for 84&#46;2&#37; and 48&#46;1&#37; of the total&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Observational studies have also confirmed the large proportion of non-CV events in HFpEF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a> There is no doubt that current findings represent a significant advance in the management of these patients&#44; however&#44; these results merit some reflections&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0015" class="elsevierStylePara elsevierViewall">HFpEF patients are generally older patients characterized by chronicity and multimorbidity&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#8211;5</span></a> Thus&#44; if we aim to decrease morbidity and mortality rather than change the mode in which patients die or are hospitalized&#44; we should recognize HFpEF as a systemic entity rather than just a cardiac issue&#46; Hence&#44; we should&#58; &#40;a&#41; improve our knowledge of the non-CV risk in these patients&#59; &#40;b&#41; increase awareness about it&#59; and &#40;c&#41; promote the creation of multidisciplinary teams to manage non-CV complications properly&#46; The overall assessment of these patients is basic&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">From a cardiac point of view&#44; we should also expand the traditional perspective of the syndrome as predominant left-sided heart disease by considering pulmonary circulation and right-sided function&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> There is a homogenous voice&#47;clamor among the scientific community moving toward precision medicine&#46; It is especially crucial in HFpEF&#44; in which the pathophysiology is widely heterogeneous&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> Along this line of thought&#44; compelling evidence points to the relevant clinical role of pulmonary hypertension and right-sided HF in HFpEF&#46; Indeed&#44; recent authors estimate that 30&#8211;50&#37; of patients with HFpEF showed PH&#47;right HF-sided phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> However&#44; it is noteworthy that neither traditional inclusion criteria nor subgroup analyses in HFpEF consider right-sided HF&#46; Indeed&#44; subgroup and post-hoc analyses of HFpEF trials mainly include the same analysis as HFrEF trials&#46; There is no data on the efficacy or safety of HF treatments according to pulmonary hypertension or right-sided HF&#46; We encourage investigators to collect this information and design further trials&#44; not ignoring the other side of the heart&#46; By looking at the heart from another perspective&#44; we may unravel different realities&#46; In a real world of older HFpEF patients&#44; a global assessment of the heart and even more important of the patient is basic&#46;</p></li></ul></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Author contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">All authors of this research paper have directly participated in the planning&#44; execution&#44; drafting the study&#59;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0030" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">All authors had no conflicts of interest to disclose&#46;</p></span></span>"
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Letter to the Editor
Light at the end of the tunnel of preserved heart failure, although important improvements are still necessary
Insuficiência cardíaca com fração de ejeção preservada – luz ao fundo túnel, apesar de ainda serem necessárias melhorias importantes
Julio Núñeza, Rafael de la Espriellaa, Francesc Formigab,
Autor para correspondência
fformiga@bellvitgehospital.cat

Corresponding author.
a Cardiology Department, Hospital Clínico Universitario de Valencia, Universitat de Valencia, INCLIVA, Valencia, Spain
b Geriatric Unit, Internal Medicine Department, Hospital Universitari de Bellvitge, IDIBELL, L’Hospitalet de Llobregat, Barcelona, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">We read with great interest the manuscript by J Silva-Cardoso et al&#46; entitled &#8220;SGLT-2 inhibitors&#58; A step forward in the treatment of heart failure with reduced ejection fraction&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> In their article&#44; the authors performed a literature review to analyze how SGLT-2 inhibitors have emerged as the fourth pillar of pharmacological disease-modifying therapy in heart failure with reduced ejection fraction &#40;HFrEF&#41; patients&#44; regardless of the presence or absence of diabetes&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">1</span></a> After a close reading of the article&#44; we would like to reflect on the current situation of heart failure with preserved ejection fraction &#40;HFpEF&#41;&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">The extensive evidence with HFrEF lack in HFpEF up to Emperor trial&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> In patients with stable HF and left ventricle ejection fraction &#62;40&#37;&#44; the Emperor trial showed a 21&#37; reduction in the primary endpoint &#40;composite of cardiovascular death or HF hospitalization&#41; at a median follow-up of 26&#46;2 months&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> This effect was mainly due to a decrease in the risk of hospitalization&#59; indeed&#44; patients on empagliflozin showed a reduction of 27&#37; in the total HF hospitalization that occurred during follow-up&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> However&#44; a neutral effect was found for all cause-mortality &#40;hazard ration &#40;HR&#41;&#58; 1&#46;00&#59; 95&#37; confidence interval &#40;CI&#41;&#44; 0&#46;87-1&#46;15&#41; and total rehospitalizations &#40;HR&#58; 0&#46;93&#59; 95&#37; CI&#44; 0&#46;85-1&#46;01&#41;&#46; Interestingly&#44; non-HF hospitalizations and non-CV-death accounted for 84&#46;2&#37; and 48&#46;1&#37; of the total&#44; respectively&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">2</span></a> Observational studies have also confirmed the large proportion of non-CV events in HFpEF patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">3&#44;4</span></a> There is no doubt that current findings represent a significant advance in the management of these patients&#44; however&#44; these results merit some reflections&#46;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0015" class="elsevierStylePara elsevierViewall">HFpEF patients are generally older patients characterized by chronicity and multimorbidity&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">1&#8211;5</span></a> Thus&#44; if we aim to decrease morbidity and mortality rather than change the mode in which patients die or are hospitalized&#44; we should recognize HFpEF as a systemic entity rather than just a cardiac issue&#46; Hence&#44; we should&#58; &#40;a&#41; improve our knowledge of the non-CV risk in these patients&#59; &#40;b&#41; increase awareness about it&#59; and &#40;c&#41; promote the creation of multidisciplinary teams to manage non-CV complications properly&#46; The overall assessment of these patients is basic&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0020" class="elsevierStylePara elsevierViewall">From a cardiac point of view&#44; we should also expand the traditional perspective of the syndrome as predominant left-sided heart disease by considering pulmonary circulation and right-sided function&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> There is a homogenous voice&#47;clamor among the scientific community moving toward precision medicine&#46; It is especially crucial in HFpEF&#44; in which the pathophysiology is widely heterogeneous&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">7</span></a> Along this line of thought&#44; compelling evidence points to the relevant clinical role of pulmonary hypertension and right-sided HF in HFpEF&#46; Indeed&#44; recent authors estimate that 30&#8211;50&#37; of patients with HFpEF showed PH&#47;right HF-sided phenotype&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">6</span></a> However&#44; it is noteworthy that neither traditional inclusion criteria nor subgroup analyses in HFpEF consider right-sided HF&#46; Indeed&#44; subgroup and post-hoc analyses of HFpEF trials mainly include the same analysis as HFrEF trials&#46; There is no data on the efficacy or safety of HF treatments according to pulmonary hypertension or right-sided HF&#46; We encourage investigators to collect this information and design further trials&#44; not ignoring the other side of the heart&#46; By looking at the heart from another perspective&#44; we may unravel different realities&#46; In a real world of older HFpEF patients&#44; a global assessment of the heart and even more important of the patient is basic&#46;</p></li></ul></p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Author contributions</span><p id="par0025" class="elsevierStylePara elsevierViewall">All authors of this research paper have directly participated in the planning&#44; execution&#44; drafting the study&#59;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Funding</span><p id="par0030" class="elsevierStylePara elsevierViewall">None&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0035" class="elsevierStylePara elsevierViewall">All authors had no conflicts of interest to disclose&#46;</p></span></span>"
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