Bioprosthetic heart valves: The last taboo - clinical evidence, ethico-legal assessments and informed consent in Muslim patients

Abstract

The recent 2025 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines for the management of valvular heart disease (VHD) state that treatment should be tailored to patient’s preferences. Durability is the main limitation of bioprosthetic heart valves (BHVs), due to structural valve degeneration and increased pannus formation. There is no definitive evidence that bovine pericardium protheses (BPP) are inferior to porcine xenografts (PX) in terms of durability. Muslim patients, due to their religious belief, may prefer to be treated with BPP rather than PX, except for Darurah (emergency) and Istihalah (physicochemical transmutation) conditions. Our paper highlights two key point. First, Italian Muslim professionals have little information concerning the presence of porcine derivatives in BHVs and regarding the existence of an alternative to PX with BPP. Second, the quality and quantity of biological material in BHVs is only known by bio-manufacturers that do not disclose this data spontaneously. To comply with the 2025 ESC/EACTS guidelines for the management of VHD, we believe that the heart team could benefit from the advice of qualified Islamic religious leaders in delivering to Muslim patients the scenario of BHV utilization with complete, relevant, and accessible information.

Key Words: Bioprosthetic heart valve; Bovine pericardial bioprotheses; Porcine xenograft; Muslim patient; Ethico-legal assessment; Informed consent; Darurah; Istihalah; Istihlaak

Core Tip: There is no definitive evidence that bovine pericardium protheses (BPP) are inferior to porcine xenografts (PX) in terms of durability. Among Muslims, there is little information on the presence of porcine derivatives in bioprosthetic heart valves (BHVs). Muslim patients may prefer BPP rather than PX, except for Darurah and Istihalah conditions. Unfortunately, the quality of biological material in BHVs is only known by bio-manufacturers. To comply with the 2025 European Society of Cardiology/European Association for Cardio-Thoracic Surgery guidelines for the management of valvular heart disease, we believe that the heart team could benefit from the advice of qualified Islamic religious leaders in delivering to Muslim patients a comprehensive scenario of BHV utilization.

INTRODUCTION

Cardiovascular medicine regularly uses substances that Islam considers impure and that should be avoided. These include medications containing alcohol and pork derivatives[1]. Nevertheless, religion is an important component of an individual’s identity, especially if they are part of a religious and/or ethnic minority group[2]. In addition, nowadays it is widely accepted that religion is one of the social determinants that may influence people’s health, cardiovascular disease and mortality[3]. However, it is not easy for persons belonging to a religious and/or ethnic minority group in a largely secularized society to respect all or most religion norms. Moreover, Islam is a holistic religion that addresses not only spiritual issues but seeks also to regulate many aspects of daily life. In the recent decades, during the whirlwind advancement of medicine, Muslim theologians tried to address the new issues to help believers comply with the religious dictates. However, narrowing down the problems has been a difficult exercise, thus resulting in ambiguous situations both for theologians as well as especially for Islamic patients[4,5]. For instance, Muslim patients are often unaware of the possibility of receiving a bioprosthetic heart valve (BHV) containing porcine derivatives. And even if they are informed, which often happens immediately before surgery, they do not know how to behave[6]. These situations create discomfort also for the healthcare workers who are being increasingly implicated in this scenario.

The recent 2025 European Society of Cardiology (ESC)/European Association for Cardio-Thoracic Surgery (EACTS) guidelines for the management of valvular heart disease (VHD) report that “patient education and information, using online material and face-to-face conversations, are essential at each step. A clearly defined point of contact for all questions relating to the disease or type of treatments should be communicated to the patient and their relatives”[7]. These guidelines state also that patient-reported outcome measures (PROMs) should be evaluated, when available, as the basis for recommendations and/or discussions, as PROM-oriented studies improve quality of life and patient satisfaction[7]. These guidelines indicated that the use of a BHV instead of a mechanical valve is recommended according to the desire of the informed patient (class I, level C)[7]. Thus, medical and surgical treatment should be tailored to ensure that also patient’s beliefs are factored into the clinical decision-making process[6,8]. And the heart team for the management of VHD could benefit of the opinion of prepared theologians to address these settings.

In this paper, we aim to address the use for Muslim patients of BHVs, particularly those containing pork derivatives.

BHVS

Worldwide, the incidence of VHD has increased. However, there are important differences. In developing countries, where rheumatic heart disease (RHD) remains the leading cause of VHD, mitral stenosis and regurgitation, and aortic regurgitation are prevalent, whereas in industrialized countries, where the primary etiology of VHD is valve degeneration, driven by an aging population, the prevalent valvulopathy is aortic stenosis[9]. Nevertheless, due to the recent uncontrolled immigration in European countries, the number of patients with VHD related to RHD is increasing[10].

BHVs differ from mechanical valves, which are mostly made of pyrolytic carbon, titanium and other metallic alloys, because they contain biological derivatives. BHVs can be classified as xenografts, allografts, or autografts. Xenografts are animal-derived (bovine, porcine, or equine). The tissue used is from animal’s cardiac valve, pericardium or jugular venous valve. Pigs are the most favored animals for xenotransplantation, as their organs are similar in size to that of human beings and they are relatively easy to breed and produce large litters several times in a year. More recently, xenografts started to be made from genetically engineered pigs to eliminate xenogeneic antigens and reduce immunologic-associated valve calcification[9,11]. Allografts are derived from human donors, mainly cadavers. Autografts involve the transplantation of a patient’s own valve from one position to another, for example from the pulmonary site into the aortic one[9,12]. Clinically, xenografts are the primary type of BHVs as the use of allografts and autografts remains restricted. Transcatheter implantable bioprosthetic valves, which are increasingly used for treating prosthetic valve dysfunction or as an alternative to surgery, are grouped into xenografts[13,14].

Mechanical valves offer longer durability; thus, they are more frequently used for patients with a longer life expectancy. On the other side, the use of BHVs has been increasingly favored over mechanical ones because they do not require lifelong anticoagulation and, thus, are more ideal for young patients (injury-prone, menstruating, or pregnant) and in patients in the developing world, where close monitoring of anticoagulation may be difficult. BHVs are preferred for patients with significant comorbidities such as diabetes and renal insufficiency[15]. Moreover, in case of malfunction, BHVs offer an important advantage over mechanical valves as they can be corrected through transcatheter valve replacement (TcVR) procedures (valve-in-valve). TcVR procedures are preferred over surgical valve placement or replacement, especially for patients of advanced age, with significant comorbidities, in higher New York Heart Association (NYHA) functional class, and at increased risk for operation or reoperation[9].

In clinical practice, BHVs fall into two broad categories: Porcine xenografts (PX) or bovine pericardium protheses (BPP). The first ones have been available since the 1970s, while the second ones became available later. The aortic site come into use in 1991, and the mitral site became accessible in 2000[16,17]. The use of PX has declined over the last decades until the introduction of TcVR for aortic valve in the early 2000s. The BHVs used in TcVR procedures are mainly made from porcine pericardial leaflets as they are 30%-40% thinner than their bovine counterparts, which helps in reducing the delivery system profile, increases the effective orifice area (EOA) and improves the hydrodynamic function[12,18].

Industries do not disclose the technology they use to treat and incorporate animal tissues within BHVs. The processing of animal valves and pericardium aims to ensure tissue biocompatibility, mechanical stability, and resistance to calcification[12].

Durability is the main limitation of all BHVs because they have a limited life span as they are prone to structural valve degeneration (SVD), which can be considered their “Achilles heel”[19]. Bovine and porcine prostheses routinely provide 10-15 years of good function. SVD rates and valve longevity have changed with design modifications and animal tissue processing[20]. Although the precise mechanisms of SVD remain unknown, it is presumed that the underlying pathological process is most likely due to the glutaraldehyde treatment, which decreases valve immunogenicity at the cost of increasing calcification[8,12]. SVD is defined as deterioration of the leaflets or supporting structures of the prosthetic valve resulting in thickening, calcification, tearing, or disruption. SVD may develop in two different ways: PX more often fail by leaflet tears leading to regurgitation, whereas BPP typically degenerate by fibrosis and calcification causing stenosis[20]. Early SVD is associated with several risk factors: Patient age, renal failure, abnormal calcium metabolism, and prosthesis-patient mismatch[21]. Recent studies have suggested that SVD is an active rather than a passive process modulated by numerous mechanisms including immune-mediated responses, endothelial damage which triggers inflammatory responses, oxidative stress, subclinical thrombosis, and dysfunctional calcium and phosphorus metabolism[8,9,12]. Another cause of BHV malfunction is pannus formation, which is part of the healing process as a host’s reaction to surgical trauma, to a foreign body, or as the product of organized thrombus formation. When pannus formation exceeds its beneficial effect as a non-thrombogenic layer covering the prosthetic valves, it can lead to valve dysfunction with stenosis and/or regurgitation[21]. SVD based on information obtained from valve reintervention or autopsy may underestimate the true incidence of SVD. On the other side, definitions solely based on the presence of high transprosthetic gradient during follow-up may overestimate the incidence of SVD, as a high gradient may be caused by severe prosthesis-patient mismatch[22]. Nevertheless, comparing SVD of different BHV types is difficult as valve design and construction and resultant EOA may differ, both between and within tissue types over subsequent models[16,23]. Potential reasons for the conflicting results of the published studies could be related to different valve models, study designs, study periods, and different patient clinical characteristics[24]. Moreover, like other commodities, prosthesis choice seems to be driven also by surgeon preference or other perceived relative advantages, many of which are driven by cost considerations and valve company marketing[25].

We have tried to find out the prices of different BHVs, but the information is difficult to obtain and varies not only between countries, but also within different regions of the same country.

AORTIC SITE

BHVs are inserted in all cardiac valves, the aortic site being the most commonly used and thus where the literature is richer. Although BPP compared to PX in the aortic position seem to have better hemodynamic characteristics such as decreased transvalvular pressure gradients, larger EOA, and improved left ventricular (LV) mass regression, the debate whether the impact of valve material choice translates into improved long-term clinical outcomes remains ongoing[19,26,27]. Survival after aortic valve replacement (AVR) seems to be rather strongly influenced by age and preoperative comorbidities such as NYHA functional class and severe preoperative LV hypertrophy[20,28]. Recent studies suggest that BPP are used more commonly than PX[29]. The most recent reviews or extensive national-level databases that compared the results between BPP and PX in AVR have shown variable results[19].

In a large Korean cohort study of Kim et al[15], the use of PX vs BPP was significantly associated with an increased risk of reoperation, even though this higher risk did not translate into better survival outcomes. Moreover, the analysis of other valve-related events, such as endocarditis, thromboembolism and hemorrhage, yielded similar results, indicating no significant differences between the two valve types. Subgroup analyses revealed that the use of BPP was associated with improved survival in patients with diabetes mellitus, whereas in patients undergoing dialysis, PX exhibited better survival. In a study with an unusual lifetime (32 years) in elderly patients undergoing isolated AVR with devices from the same manufacturer, BPP provided enhanced long-term survival benefits over PX without any increase in operative mortality[30]. In a retrospective study utilizing an institutional database from 2010 to 2020, Yousef et al[31] sought to compare short- and long-term outcomes in a propensity-matched cohort of patients undergoing isolated AVR with BPP vs PX, and found comparable postoperative outcomes, long-term survival, and freedom from reintervention and readmission. Similarly, in a Swedish population-based study including all patients who had undergone AVR with any valve type from 1995 to 2012 (n = 12845; PX AVR, n = 4198; BPP AVR, n = 8647), patients receiving PX had a higher rate of reoperation compared with BPP. However, at 15-year follow-up, PX were associated with a significantly lower risk of all-cause mortality, although this difference was no longer significant in isolated AVR procedures. There was no significant difference in the risk of heart failure hospitalization between the two groups[18]. Hickey et al[16], using a national registry of 38 040 AVR collected in hospitals in England and Wales between 2003 and 2013, found nearly identical in-hospital mortality, mid-term survival and reintervention-free survival for BPP and PX. Similarly, Glaser et al[23] in a systematic review and meta-analysis found that after AVR there was no significant difference in all-cause mortality between patients who received either a BPP or a PX.

MITRAL SITE

The mitral valve is the second site most treated with valve replacement or TcVR. As with the aortic valve, at the mitral site, BHVs are preferred over mechanical valves due to thromboembolic and bleeding complications related to anticoagulation regimens[31]. Nevertheless, mitral BHVs carry a significant risk of thromboembolic complications, particularly in the early postoperative period when complete endothelialization has not yet occurred, especially in patients with concomitant atrial fibrillation[32]. Mitral BHVs tend to be less durable than aortic BHVs. This may be partially related to the higher closing pressure at the mitral position compared with the aortic site[33]. In the mitral position, the patient-prosthesis mismatch is less significant than in the aortic site[34]. There are more limited data on SVD in mitral BHVs compared to those in the aortic position because the mitral valve is more amenable to repair. In fact, in case of malfunction the indication is to repair, rather than to replace. Another reason is related to the fact that patients requiring mitral valve replacement (MVR) have poorer survival than those undergoing AVR and they die prior to experiencing valve deterioration or dysfunction[35]. SVD in the mitral position is related to leaflet tears, calcification, fracture and stent creep, which may lead to re-emergence of symptoms negatively affecting prognosis and necessitating reintervention[33]. Although BPP compared to PX in the mitral position seem to have better hemodynamic characteristics, the literature has shown variable clinical results[19,27,28].

In a recent systematic review comparing BPP vs PX for MVR, minimizing confounding factors such as variations in surgical contexts, surgeon expertise, and patient demographics, Kajitani et al[8] evaluated nine studies comprising 6945 patients with follow-up periods ranging from 3.5 years to 15 years. Although both BPP and PX exhibited acceptable mid- to long-term durability, differences in the pattern and timing of SVD were evident: Three studies favored PX, two favored BPP, and four showed no significant difference in SVD. PX failure was frequently due to leaflet tearing resulting in acute regurgitation, while BPP predominantly exhibited calcification leading to stenosis. Nevertheless, despite variability across studies, cumulative evidence suggests a trend toward superior long-term durability of PX[8]. In a meta-analysis from 20 studies published since 2010, to reflect the use of newer generation valves, Koulouroudias et al[33] found no differences in valve durability or survival between PX and BPP. A multicenter analysis evaluating long-term survival and risk of reoperation in patients undergoing BPP vs PX MVR, found no significant difference in perioperative complications, long-term survival, or risk of reoperation regardless of valve type. The authors suggested that medical comorbidities of the different cohorts may have played a role in the difference in longevity in the single studies[34]. Han et al[35], in a period between 1996-2018, compared the long-term performance of BPP and PX for MVR and found no significant differences in overall survival, risks of mitral reoperation and development of SVD between the two valve types. Similarly, Kim et al[36] demonstrated that the cumulative incidence of SVD was not different after BPP vs PX MVR over an 18-year postoperative follow-up period and that long-term clinical outcomes, including survival and mitral valve-related events, were not significantly different between the two prosthesis types. Fu et al[37] demonstrated that although BPP and PX for MVR provided satisfactory clinical results, the hemodynamic outcomes of BPP were superior to PX by achieving lower gradients and larger EOA. In the series of bioprosthetic MVR of Beute and colleagues, SVD requiring reoperation occurred earlier, and more frequently, in BPP compared to PX when implanted in patients < 65 years of age, whereas there was no difference in outcome in patients aged 65 years or older[38].

TRICUSPID SITE

The right side of the heart is a low-pressure system, and this seems to mitigate the progression of SVD of BHVs in the tricuspid and pulmonary position[39].

The preferred technique for the treatment of tricuspid valve disease is valve repair as it provides better early and long-term outcomes than tricuspid valve replacement (TVR)[40]. TVR is performed in selected patients unsuitable for valve repair or in case of failed repair. TVR is a relatively high-risk procedure due to the complex medical and/or surgical profile of patients[40,41]. TVR with BHVs is a more recent and less frequently performed procedure compared to AVR and MVR. Thus, literature data on BHVs in the tricuspid position are scarce and long-term durability of BHVs in current clinical practice has been poorly investigated. Moreover, few patients survive long enough to experience SVD.

In a systematic review comparing mechanical valve prostheses vs BHVs in the tricuspid position, both types of prostheses were found to perform equally well, even though mechanical valves had a 6-fold higher risk of thrombotic and thromboembolic complications[41]. In contrast, in a meta-analysis of Sá et al[42], TVR with mechanical valves compared with BHVs was associated with better overall survival in the long term, lower risk for reoperation, and a downward trend for risk of all-cause death in populations with larger proportions of atrial fibrillation. In a recent systematic review of studies published over the last 20 years on long-term outcomes of tricuspid BHVs, Zancanaro et al[41] found that there was a large heterogeneity in the definition and ascertainment of SVD and that the related information was inconsistently reported. Age at implantation was the strongest known independent predictor of BHV longevity. In a study comparing the performance of BPP vs PX, the use of PX had a lower cumulative incidence of reoperation, although operative mortality and early clinical outcomes were comparable and no differences were reported between BPP and PX TVR in long-term clinical outcomes, including all-cause mortality, cardiac death, ischemic stroke, hemorrhagic stroke, and endocarditis[40].

PULMONARY SITE

The pulmonary valve is the least commonly replaced heart valve. Mechanical valves are usually avoided in the pulmonary position due to a high risk of thrombosis[43]. No bespoke surgical prosthesis is available for the pulmonary position, and surgeons implant prostheses designed for the aortic position as an off-label procedure[44]. Thus, outcome data on BHVs in the pulmonary position are sparse.

According to Bond et al[44], in England and Wales surgeons favour BPP, although there is some observational evidence that PX may last longer, especially in younger patients. In a bicentric propensity-matched analysis, both bioprostheses had similar outcomes during the first 5 years. Beyond 5 years, there was no difference in the rate of reintervention, although PX had less SVD than BPP[45]. Similarly, in a large case-series of patients undergoing stented bioprosthetic pulmonary valve replacement, no clear superiority of one type of bioprostheses was demonstrated[44]. In contrast, in a study of Kwak et al[46] in patients with congenital cardiac anomalies, PX compared with BPP had long-term advantages in terms of reduced reoperation rate and SVD in the pulmonary position.

ISLAMIC RELIGION AND BHVS

Muslims are the world’s second-largest religious group and the fastest-growing major religion. In 2020, it accounted 2 billion subjects (25.6% share of the world’s population)[47]. In Europe, in the second part of the 20^th century and at the beginning of the 21^st century, the immigrant Islamic population has become a structural feature of the European society. Reliable information on the religion of European citizens, of immigrants legally or illegally residing in Europe, and of refugees is challenging to obtain because it is considered sensitive data[48]. According to the Pew Research Center analysis, Muslims made up 6% (45.5 million people) of the European population in 2020[48], and under a medium migration scenario are projected to rise to 11.2% (58 million) by 2050[49].

In Italy, a country with historically strong Catholic tradition, Islam represents the second largest religious group (29.8% of total immigrants, approximately 1.6 million), following Christians (53%)[50,51]. This number does not include Muslims with Italian citizenship, ranging from 600000 to one million people[52]. Thus, the total Muslim population in Italy is estimated to be approximately 2.5 million people. In Italy, under a medium migration scenario, Muslims are expected to rise from the current level of 4.4% to 12.4% (7 million people) by 2050[50]. More than half of Italian Muslims are of Moroccan, Albanian, and Bangladeshi descendent[51]. Shiites are a minority group (< 5%), being most Italian Muslims Sunni, once predominantly Arabs, but with an increasing shift in its composition because of the arrival of sub-Saharan and south-eastern Asian Muslim communities[52].

In Italy, as in the rest of Europe, the majority of those who have a religious affiliation are non-practicing, and the number of non-believers is higher, especially among youth autochthons[53].

According to the Islamic religion, the only reason for which Allah created humans is to adore him. “I did not create jinn and humans except to worship me; I seek no provision from them, nor do I need them to feed me” (Qur’an 51: 56-57). He sent prophets and sacred books to teach humans how to adore him. These teachings are found in the Qur’an, the last sacred book, and in the Sunnah, which is based on the words and acts of the last prophet Muhammad (peace and mercy of Allah upon him) recorded in collections of narrations called hadith. The Shari’ah is a legal set derived from these teachings, while Fiqh represents the human understanding of Shari’ah. According to the Shari’ah, any porcine product is forbidden (ḥarām). The Qur’an states that “he has only forbidden to you carrion, blood, and the flesh of swine” (Qur’an 2: 173). Furthermore, it is permitted (halāl) to use products derived from other animals like bovine only if they are slaughtered strictly according to Shari’ah. The Qur’an states that “he has only forbidden...what is slaughtered in the name of any other than Allah” (Qur’an 5: 3). These conditions may limit the therapeutic options for Muslims as in modern medicine many ingredients or aiding substances are derived from pigs and cattle. Prophetic traditions state that unlawful substances should not be used for treatment: “Verily, Allah sent down the disease and the cure, and for every disease he made a cure. Seek treatment, but do not seek treatment by the unlawful” (Source: Sunan Abī Dāwūd 3874; In-book reference: Book 29, Hadith 20; English translation: Book 28, Hadith 3865). The common porcine and bovine-based ingredients are gelatin, collagen, stearic acid, insulin, pancreatic enzymes, anticoagulants, heparin and tissues (cardiac valves, pericardium). Thus, the use of these ingredients, which are present in more than 1000 medications, may create an ethical dilemma to those who believe as their use is an act that contravenes their believing and could be considered even as a sin[1,4,15].

Religious systems are continuously asked to revisit their traditional ethico-legal codes, to dialogue with the scientific advancements of modern biomedicine and to provide guidance and practical counsels for contemporary society[4]. Nevertheless, those who study Shari’ah and Fiqh state that there is not a Manichaean division between halāl and ḥarām. In fact, in the medical setting, there are other conditions that should be considered. The first consideration is that when Muslims suffer from illness, seeking medication is mandatory[4,15]. In fact, according to the Shari’ah seeking medical treatment in life-threatening situations is not just encouraged but becomes obligatory. This principle is consistent with the Qur’anic emphasis on the preservation of life: “Do not kill yourselves; indeed, Allah is ever merciful to you” (Qur’an 4: 29).

The other two conditions are darurah situation, and istihalah and/or istihlaak[15]. Darurah (state of emergency) is a situation when there is harm or risk that can lead to death. For instance, darurah can happen when one must use medications that contain ḥarām sources in conditions where halāl medications are not available and his/her health will be at real risk if he/she does not take the medications containing ḥarām ingredients. The principle of necessity is firmly rooted in Islamic jurisprudence and scripture: “But if someone is compelled by necessity—neither driven by desire nor exceeding immediate need—then surely your Lord is all-forgiving, most merciful” (Qur’an 6: 145).

Istihalah (transmutation) is a condition where there is a transformation, either physical (involving its properties and characteristics such as odor, taste, and color) or chemical (change in chemical substances). Not all Sunni jurisprudential schools accept that the istihalah process can change a material from a ḥarām to a halāl one. The physical and chemical transmutation can determine the occurrence of a real change in the defiled or Shari’ah-banned material leading to its conversion to another material that differs from the original one in characteristics and attributes[54-56]. Istihalah can occur spontaneously like the passage from grape juice to wine and eventually from wine to vinegar. The istihalah process does not permit the use of wine, which is the result of the alcoholic fermentation of grape juice, because it contains ethanol (ḥarām). Whereas the transformation of ethanol to acetic acid permits the use of vinegar, as acetic acid is halāl. Istihalah can occur also by direct human intervention.

Istihlaak (dilution) is the loss of properties and characteristics of the original material because of immersion into a larger quantity of pure material in such a way that the characteristics and attributes of the submersed material completely vanish and the material is no longer identifiable in any of its different forms[15,54-56].

It is necessary to have a religious ethico-legal opinion or clarification (fatwā, pl. fatāwā) issued by recognized juridical body, or qualified jurisconsults to permit the use of ḥarām medications in case halāl medicines are not available and/or to state that ḥarām medications have gone through the istihalah or istihlaak process. Usually, the recognized juridical body or qualified jurisconsults consult thematic experts before issuing a fatwā. In the field of medicine, the consulted experts are physicians, surgeons, nurses, pharmacologists, chemists, economists, and those who are involved in the bio-industrial process. The list of terms used in this article (which may be unfamiliar to non-Muslim professionals) is provided in the Supplementary material.

EMPIRICAL RESEARCH

In this article, we aimed to contribute to the empirical data exploring knowledge and attitudes of Muslim patients toward pig derivatives, particularly in relation to the use of BHVs. This exploratory pilot study provides preliminary insights, and its findings should be interpreted in light of the sample characteristics.

To the best of our knowledge, this is the first paper on how Muslims interact specifically with BHVs. We conducted a cross-sectional study on almost all members of the Professionisti Musulmani (PROMUS) association, which is the most recent Italian Islamic association operating at a national level. PROMUS members work in various fields, have different level of education and religious observance. All members were informed on the subject matter of the study (BHVs). A questionnaire in Italian was posted on the social media with the aim at obtaining answers on the level of knowledge among PROMUS members of Islam’s rulings on the use of BHVs.

The 25 out of 301 (8%) subjects did not reply to the questionnaire. Among respondents (n = 276; median age 27.2 years; range 16-70 years), 81 subjects (29.3%) were first-generation immigrants while the rest were born and raised in Italy; 195 were female (70.6%); 126 (45.6%) had a university degree, 5 of whom a PhD, and 143 (51.8%) had a secondary degree. One hundred and eighty-seven (67.7%) of the participants referred to have an average level of religious knowledge, whereas those who reported to have a high or very high level of religious knowledge were 59 (21.4%), and only few participants reported having a low level of religious knowledge (n = 30, 10.9%). Almost half of the participants knew that porcine-derived material was used during heart valve replacement (51.4%). Most of the respondents did not know if, according to the Islamic religion, it is allowed to implant a PX in a Muslim patient (n = 175, 63.4%), whereas 45 (16.3%) and 56 (20.3%) answered that it was permitted or not permitted, respectively. Surprisingly, most of the respondents did not know that there was an alternative to the PX (65.9%) and did not know that there was the possibility of implanting a BPP (73.2%). Nevertheless, most of the participants were aware that in an emergency it is possible to operate a patient with a PX (74.6%) (Table 1).

Table 1 Professionisti Musulmani members’ knowledge regarding Islam and bioprosthetic heart valves, n (%).

Some questions in the online questionnaire	Yes	No	Don’t know	Total
Did you know that some BHVs contain porcine material?	142 (51.4)	134 (48.6)	0 (0.0)	276 (100)
According to the Islamic religion is it permissible to transplant a PX in a Muslim patient?	45 (16.3)	56 (20.3)	175 (63.4)	276 (100)
Did you know of the existence of valid alternatives of other animal origin to the PX?	94 (34.1)	182 (65.9)	0 (0.0)	276 (100)
Did you know that bovine and equine BHVs are a valid alternative to PX?	74 (26.8)	202 (73.2)	0 (0.0)	276 (100)
According to the Islamic religion is it permissible to transplant a PX in a Muslim patient in emergency, in absence of other BHV alternative?	206 (74.6)	3 (1.1)	67 (24.3)	276 (100)

BHV: Bioprosthetic heart valve; PX: Porcine xenograft.

DISCUSSION

The so far analyzed literature demonstrates that in cardiac valve replacement procedures with BHVs, except for specific cases, BPP are at least not inferior to PX in all four heart valve locations. In fact, it seems there is no clear superiority of PX vs BPP in terms of SVD, survival outcomes, increased risk of complications or reoperation. Therefore, it is desirable to offer to Muslim patients who request it the possibility of being treated with a BPP. Some concern exists for the TcVR procedures where porcine pericardial valves are preferable as they are 30%-40% thinner than their bovine counterparts, which helps in reducing the delivery system profile, increases the EOA and improves the hydrodynamic function[12,19].

Our study highlights two key points. First, similarly to what have been reported by others in larger, but more diverse populations, our data on qualified PROMUS members confirm that information regarding the presence of porcine derivatives in BHVs and the existence of an alternative with BPP is scarce. In fact, many if not most Muslims worldwide are not aware that some medications they need to take contain ingredients that are ḥarām[4]. There are reports of patients who stopped their medication when they knew that it contained porcine-derived ingredients[1]. Likewise, not all Imams (Muslim clergymen) or Muslim physicians are aware of the debate surrounding the fatāwā that have been issued regarding the use of animal-derived materials[15]. Second, unfortunately, the most interesting information for us in this setting is missing: How much of the biological material is present in BHVs and if it can be traced back to the original animal tissue. Given that this information cannot be easily obtained, it complicates the fatwā process.

Therefore, much needs to be done within the Islamic communities to instruct both patients and Imams. It is important that those who are in charge in issuing fatāwā have the correct information, especially from bio-industries, to deliver their ethico-legal assessments to their religious adherents on the ground[4]. The authors of this paper agree with the proposal of Bokek-Cohen et al[6] to consider adding an informed consent form for biological devices in line with the good medical practice and patient-centered care. Finally, it is essential that healthcare workers alongside with prepared Islamic community religious leaders deliver to the patients the correct scenario of the utilization of BHVs with complete, relevant, and accessible information, as this is also part of the recent 2025 ESC/EACTS guidelines[7].

CONCLUSION

There is no definitive evidence that PX are superior to BPP in terms of durability. Muslim patients, due to their religious belief, may prefer to be treated with BPP rather than PX, except for Darurah (emergency) and Istihalah (physicochemical transmutation) conditions. Unfortunately, Muslim patients have little information concerning the presence of porcine derivatives in the BHVs and regarding the existence of an alternative to PX with BPP. Moreover, the quality and quantity of biological material in BHVs is only known by bio-manufacturers that do not disclose this data spontaneously. To comply with the 2025 ESC/EACTS guidelines for the management of VHD, which state that treatment should be tailored to patient’s preferences, we believe that the heart team could benefit from the advice of qualified Islamic religious leaders in delivering to Muslim patients the scenario of BHV utilization with complete, relevant, and accessible information.

ACKNOWLEDGEMENTS

We wish to thank Dr. Amen Al-Hazmi and Dr. Aref Al Galal, theology teachers at the Italian Institute for Islamic and Humanistic studies - BAYAN, for their contribution in clarifying the ethico-legal assessments of bioprosthetic heart valves. We wish also to thank Dr. Giovanni Braccini and Ing. Hamza Lahbibi who reviewed the statistical methodology, as well as Prof. Annarosa Arcangeli and Prof. Federico Carpi who provided valuable feedback.