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Challenges in patients living with HIV: The sudden cardiac death conundrum
Desafios em doentes com HIV: o problema da morte súbita cardíaca
Cardiology Department, Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal
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"apellidos" => "Garrido" ] 1 => array:2 [ "nombre" => "João" "apellidos" => "Borges-Costa" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204920301549?idApp=UINPBA00004E" "url" => "/21742049/0000003900000003/v1_202010170733/S2174204920301549/v1_202010170733/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S2174204920301586" "issn" => "21742049" "doi" => "10.1016/j.repce.2019.04.002" "estado" => "S300" "fechaPublicacion" => "2020-03-01" "aid" => "1507" "copyright" => "Sociedade Portuguesa de Cardiologia" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Rev Port Cardiol. 2020;39:155-60" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original 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"nombre" => "Süleyman Sezai" "apellidos" => "Yıldız" ] 4 => array:2 [ "nombre" => "Kudret" "apellidos" => "Keskin" ] 5 => array:2 [ "nombre" => "Serhat" "apellidos" => "Sığırcı" ] 6 => array:2 [ "nombre" => "Ali" "apellidos" => "Bayraktar" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2174204920301586?idApp=UINPBA00004E" "url" => "/21742049/0000003900000003/v1_202010170733/S2174204920301586/v1_202010170733/en/main.assets" ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Commentary</span>" "titulo" => "Challenges in patients living with HIV: The sudden cardiac death conundrum" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "161" "paginaFinal" => "162" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Bruno Rocha, Carlos Aguiar" "autores" => array:2 [ 0 => array:2 [ "nombre" => "Bruno" "apellidos" => "Rocha" ] 1 => array:4 [ "nombre" => "Carlos" "apellidos" => "Aguiar" "email" => array:1 [ 0 => "ctaguiar@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Cardiology Department, Hospital de Santa Cruz, Centro Hospitalar Lisboa Ocidental, Lisboa, Portugal" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Desafios em doentes com HIV: o problema da morte súbita cardíaca" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Early in the epidemic of human immunodeficiency virus (HIV), opportunistic infections related to acquired immune deficiency syndrome (AIDS) inevitably led to death and palliative care was the rule. Fortunately, effective therapy emerged during the so-called highly active antiretroviral era, leading to improved survival. Nowadays, the long-term care of people living with HIV/AIDS (PLWHA) has led to increased focus on the chronic management of comorbidities, particularly those related to the aging of the HIV-infected population and to cardiovascular disease (CVD). While acute life-threatening cardiac manifestations (especially infective endocarditis, myocarditis and pericarditis) dominated the clinical picture in the early HIV epidemic, premature atherosclerosis and its consequences are currently the leading cardiovascular presentation of PLWHA.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">1–3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the survival of well-managed PLWHA on antiretroviral therapy is now comparable to that of healthy controls, deaths due to CVD have been proportionately increasing in the former.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">4</span></a> Several mechanisms may be responsible, including a higher prevalence of traditional cardiovascular risk factors in HIV-infected patients than in age- and gender-matched controls, a chronic inflammatory state and low-grade systemic inflammation even in patients with apparently controlled HIV infection, atherothrombotic risk factors, and adverse events related to combined antiretroviral therapy.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">1</span></a> These may account for the pervasiveness of coronary artery disease (CAD), microvascular disease, heart failure (HF) and atrial fibrillation, among others, in PLWHA.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Surprisingly, a large study by Tseng et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> enrolling 2860 consecutive PLWHA showed that, over a median 3.7 years of follow-up, non-AIDS mortality was mostly due to sudden cardiac death (SCD), which accounted for 86% of all cardiac deaths. These patients had a higher prevalence of prior myocardial infarction compared to those who had a non-SCD (17% vs. 1%, p<0.0005). The mean SCD rate reported was 2.6 per 1000 person-years over a 10-year period. Moreover, Mongardon et al.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">6</span></a> retrospectively assessed 99 PLWHA successfully resuscitated after cardiac arrest, and demonstrated that a third of these were due to a cardiac cause, roughly half of which were clearly unrelated to myocardial infarction. In addition, these authors suggested that outcomes were not associated with HIV status (i.e., CD4 and viral counts), as per propensity-score matching to a control cohort with a similar presentation.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Altogether, the available evidence supports the idea that SCD occurs at a higher rate than expected in PLWHA. This may be due to various factors that are yet to be elucidated,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">7</span></a> which may include the following:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">•</span><p id="par0025" class="elsevierStylePara elsevierViewall">Host-related factors: increased atherogenic burden and SCD as a manifestation of CAD and HF. However, it has been suggested that SCD has a higher incidence than would be expected solely as a direct consequence of the aforementioned clinical scenarios; additionally, substance abuse (particularly amphetamines and alcohol) may also play a role;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">•</span><p id="par0030" class="elsevierStylePara elsevierViewall">HIV-related factors: mechanisms may include systemic inflammation leading to rapidly progressive CAD, featuring vulnerable plaques known to be associated with a higher risk of atherothrombotic events and arrhythmogenic manifestations; in addition, HIV-related rhythm disturbances that may be the result of electrical cardiac remodeling and prolonged QTc due to autonomic dysfunction, may also facilitate SCD;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">•</span><p id="par0035" class="elsevierStylePara elsevierViewall">Treatment-related factors: several drugs used in PLWHA (such as lopinavir-ritonavir, trimethoprim-sulfamethoxazole and methadone) are associated with both metabolic derangements and acquired prolonged QTc interval (hence torsades de pointes); furthermore, hypokalemia, hypomagnesemia and hypocalcemia are frequently found in HIV-infected patients, often as a consequence of drug-related diarrhea, gastrointestinal opportunistic infections and/or HIV enteropathy.</p></li></ul></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is indisputable that SCD is worrisome in PLWHA and may account for many (if not most) premature and late deaths. As of now, we lack tools that can predict SCD risk in PLWHA and that may guide effective prevention. Other than systematically measuring QTc interval, particularly when introducing QTc-prolonging drugs, and selecting patients who may benefit from an implantable cardioverter-defibrillator (ICD), no other interventions are known to prevent arrhythmic SCD in HIV-infected patients. Moreover, identification of PLWHA with HF who may benefit from an ICD as primary prevention is done by extrapolating data from HF trials that have not properly addressed HIV-related cardiomyopathy. There are too many unknowns, and there is a need for urgent action in a matter of utmost importance.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The current issue of the <span class="elsevierStyleItalic">Journal</span> sees the publication of a single-center prospective case-control study of 89 PLWHA (antiretroviral therapy in 74% and controlled viral counts in 53%) and 62 age and gender-matched healthy controls.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> Cetina et al. found that PLWHA had significantly increased Tp-e (measured from the peak to the end of the T wave) and corrected Tp-e (Tp-ec) intervals, as well as a higher Tp-e/QT ratio, in comparison to controls. Furthermore, these variables had a moderate but significant inverse correlation with CD4 T-cell counts. These findings add to the known increased risk of SCD in HIV-infected patients,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">5</span></a> but also extend it to those with apparently controlled infection (as per CD4 T-cell counts and viral loads). Moreover, they unveil a potential role in PLWHA for easily measured electrocardiographic markers known to be linked to arrhythmogenic burden and SCD.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Tp-e interval, Tp-ec interval and Tp-e/QT ratio, indices of repolarization heterogeneity, have been shown to be increased in several clinical scenarios in comparison to healthy controls, such as in pediatric patients with dilated cardiomyopathy,<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">9</span></a> acute myocarditis<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">10</span></a> and sleep apnea,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">11</span></a> to name a few, and it has been suggested that they may indicate increased SCD risk. Future investigations should focus on large studies with long-term follow-up to elucidate whether these markers may aid in arrhythmogenic stratification of PLWHA and, ultimately, facilitate interventions to further improve management in a population already at higher risk of both atherogenic and SCD events. In addition, the question whether QTc prolongation due to HIV treatment and known pathophysiological mechanisms shared with premature CAD play a major role in SCD is worth investigating further.</p><p id="par0055" class="elsevierStylePara elsevierViewall">In conclusion, the shift of HIV from a life-threatening acute condition to a chronic manageable disease, in parallel with the aging of PLWHA, has led to a new paradigm of increased need to focus on treating related comorbidities and to draw on a wide range of medical specialties, especially cardiology, oncology, and geriatric medicine. Finally, the role of the cardiologist caring for PLWHA not only includes prevention of cardiovascular risk factors to mitigate atherogenic burden but may also extend, in the future, to SCD prevention once suitable tools are available to enable appropriate risk stratification to be integrated into clinical practice. The present study<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">8</span></a> adds a small but important piece to the puzzle of SCD in PLWHA.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Conflicts of interest</span><p id="par0060" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflicts of interest" ] 1 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0060" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Future challenges for clinical care of an ageing population infected with HIV: a modelling study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:3 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 4 | 11 |
| 2024 October | 52 | 34 | 86 |
| 2024 September | 61 | 26 | 87 |
| 2024 August | 51 | 33 | 84 |
| 2024 July | 36 | 39 | 75 |
| 2024 June | 29 | 22 | 51 |
| 2024 May | 32 | 24 | 56 |
| 2024 April | 32 | 27 | 59 |
| 2024 March | 38 | 23 | 61 |
| 2024 February | 25 | 24 | 49 |
| 2024 January | 26 | 20 | 46 |
| 2023 December | 26 | 30 | 56 |
| 2023 November | 38 | 40 | 78 |
| 2023 October | 19 | 11 | 30 |
| 2023 September | 23 | 18 | 41 |
| 2023 August | 20 | 19 | 39 |
| 2023 July | 24 | 12 | 36 |
| 2023 June | 26 | 15 | 41 |
| 2023 May | 40 | 38 | 78 |
| 2023 April | 28 | 4 | 32 |
| 2023 March | 49 | 17 | 66 |
| 2023 February | 28 | 19 | 47 |
| 2023 January | 22 | 14 | 36 |
| 2022 December | 42 | 16 | 58 |
| 2022 November | 32 | 28 | 60 |
| 2022 October | 52 | 34 | 86 |
| 2022 September | 30 | 33 | 63 |
| 2022 August | 28 | 31 | 59 |
| 2022 July | 28 | 43 | 71 |
| 2022 June | 25 | 32 | 57 |
| 2022 May | 23 | 24 | 47 |
| 2022 April | 35 | 44 | 79 |
| 2022 March | 31 | 43 | 74 |
| 2022 February | 43 | 35 | 78 |
| 2022 January | 47 | 22 | 69 |
| 2021 December | 38 | 37 | 75 |
| 2021 November | 32 | 34 | 66 |
| 2021 October | 41 | 45 | 86 |
| 2021 September | 23 | 25 | 48 |
| 2021 August | 34 | 33 | 67 |
| 2021 July | 26 | 28 | 54 |
| 2021 June | 27 | 25 | 52 |
| 2021 May | 23 | 46 | 69 |
| 2021 April | 61 | 39 | 100 |
| 2021 March | 30 | 28 | 58 |
| 2021 February | 34 | 21 | 55 |
| 2021 January | 25 | 14 | 39 |
| 2020 December | 33 | 17 | 50 |
| 2020 November | 20 | 15 | 35 |
| 2020 October | 18 | 5 | 23 |
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