Abstract 

The current research is based on Arrhythmogenic Right Ventricular Dysplasia and the various aspects associated with the fatal clinical condition. A descriptive research background and rationale for the study has been provided. Furthermore, the aims and objectives of the research have also been depicted in vivid details, the research questions have been prepared aligned with that. Along with that the problem statement and the significance of the study procedure has been depicted as well. A brief overview of Arrhythmogenic Right Ventricular Dysplasia has been stated in the literature review chapter along with the different types of the disease and their genetics. The potential strategies associated with the accurate detection of the disease have been provided here as well. The pharmacological and non-pharmacological treatments in terms of ARVD have been stated. The results and discussion chapter discusses some other aspects associated with the disease along with the model for minimising the disease risk. A brief acknowledgement has also been provided at the end of the research project.

 

Chapter 1: Introduction

1.1. Research Background 

Arrhythmogenic Right Ventricular Dysplasia, abbreviated as ARVD can be depicted as a more or less rare form of genetic cardiomyopathy within the individuals. As the name suggests, the disease is preliminary known to affect the right ventricle (RV) of the patients, however, in some circumstances, it is known to affect the left ventricle (LV) as well. The disease is quite rare in terms of medical syndromes and is generally known to affect the younger population. The current research is based on the assessment and evaluation of the different types of Arrhythmogenic Right Ventricular Dysplasia, their potential symptoms, techniques and technologies incorporated within their detection method and its treatment procedure. The topic was taken into consideration due to its rarity and occurrence in the younger section of population. It has further been included based on the hereditary aspects associated with the initiation of the disease as well.

1.2. Rationale for Study 

Arrhythmogenic Right Ventricular Dysplasia can be identified as a medical condition of autosomal inheritance where heredity is known to play quite a major role in the occurrence of the disease. The syndrome is generally known to occur in a comparatively younger population and can be majorly fatal among the patients. According to Orgeron et al. (2017), the disease is often known to prompt life-threatening ‘ventricular arrhythmias’ prompting sudden cardiac arrests leading to deaths. The estimated prevalence of the disease has been witnessed to increase considerably among the general population. The ratio of the disease occurrence is estimated to be 1:5000 (Sagepub.com, 2021). It has been further detected that the chance of occurrence of the disease among the males are comparatively higher than that of the female population. Arrhythmogenic Right Ventricular Dysplasia is further characterised by the occurrence of various pathological conditions including the cardiac atrophy, fibro fatty replacement, fibrosis and the thinning of the inner lining of the cardiac muscles due to the dilation of the cardiac chambers and the formation of constant aneurysms. 

The sustainable escalation of the disease especially among the younger generation is considered to be the prime rationale on behalf of the occurrence of the disease condition. The on growing occurrence of the disease and its potentially fatal consequences can also be identified as the potential rationale associated with the conductance of the research process. 

1.3. Research Aim 

The prime aim of the research associated with the research is to accurately determine the incidents of Arrhythmogenic Right Ventricular Dysplasia along with its clinical manifestations, diagnosis process as well as associated treatment procedures. 

1.4. Research Objectives 

The prime objective of the research can be depicted as follows:

• To identify an overview of Arrhythmogenic Right Ventricular Dysplasia (ARVD)
• To evaluate the different types of ARVD  and their associated genetics
• To analyze the potential strategies associated with the detection of ARVD
• To recommend the pharmacological and non-pharmacological treatments of the ARVD

1.5. Research Questions

The research questions can be stated as follows:

• What is the comprehensive overview of ARVD?
• What are the different types of ARVD and what are their associated genetics?
• What are the potential strategies related to the detection of ARVD?
• What are the pharmacological and non-pharmacological treatments associated with the syndrome of ARVD?

1.6. Problem Statement

The disease of ARVD is known to be quite uncommon and does possess an occurrence rate of almost 1 in 5000 individuals. The research provides emphasis towards the betterment of the research process in order to accurately detect and determine the potential clinical manifestations associated with the disease. The epidemiology of the disease is further known to include a major cardiac atrophy, fibro fatty replacements, fibrosis and various other conditions that may be often difficult to determine and assess. Furthermore the disease of ARVD is also known to possess various ethnic variations including the different models and patterns of gene inheritance. All these factors and aspects are further known to make the disease more complicated in nature. The research hopes to provide focus towards the genres and the clinical manifestations involved in the disease, as well as the potential treatments that are necessary for the sustainable treatment of the medical condition over the progress of time.

1.7. Significance and Scope of the Study

A sustainable understanding regarding the topic will provide the researchers with a comprehensive knowledge regarding the medical condition and the potential occurrences of the disease. It will also help to acquire vivid information related to the treatment patterns and strategies to be incorporated for the mitigation of the disease symptom. A definite idea regarding the mode of instances of the clinical condition, their pathogenic mechanisms, age at presentation and the potential progression timing of the disease can further be assessed and evaluated. The significance of the study further lies in the fact that the clinical practitioners and the common people will tend to become relatively more aware regarding the disease syndrome that will further provide with a better scope of research.

Chapter 2: Literature Review 

2.1 Overview of Arrhythmogenic Right Ventricular Dysplasia 

Arrhythmogenic Right Ventricular Dysplasia (ARVD) is one of the rare diseases or a critical type of cardiomyopathy where the fat and fibrous tissues replace the right ventricle muscles within the heart. It can be stated that the contraction and dilation of the right ventricle is poor due to the fat or fibrous blockage. This cardiovascular disease can cause life threatening situations which are “Sudden Cardiac Death (SCD)”, Ventricular Arrhythmias and “Biventricular heart failure” (Wang et al. 2019). The electrical signals which are received and transferred through the human heat are disrupted through ARVD. These disruptions within the cardiovascular areas of the body result in arrhythmias. Some of the symptoms of this disease include disrupted heart rhythms, sudden arrest, chest palpitations, fainting, breath shortness and dizziness. 

Arrhythmogenic Right Ventricular Dysplasia can be pathologically by fibro fatty replacement, myocardial atrophy and fibrosis. It can be stated that the changes due to ARVD generate the consequences of Ventricular Tachycardia. It has been observed that this cardiovascular disease is diagnosed among young athletes and healthy populations. This is one of the complex cardiomyopathy that is not recognisable and results in sudden death of an individual. Moreover, it can be also stated that this disease is dependent on the genetic or inheritance mode of an individual. The diagnosis of this disease is mainly based on multiple suspections which are syncope, palpitations, cardiac arrest. The investigations and diagnosis of this cardiovascular disease is also dependent on family history, cardiography, angiography and other imaging evaluation techniques. 

2.2 Different types of ARVD and its genetics 

The causes or reason behind the occurrence of ARVD is complex and unknown. It has been mentioned earlier that family history and genetic inheritance are taken into account in terms of diagnosing the presence of ARVD. On the contrary, it has been also observed that the patients with ARVD have no past family histories or genetic influences which reflects a complex reason behind this cardiovascular disease. Due to the lack of effective symptoms and areas of diagnosis, ARVD has been classified into two different types as per its inheritance pattern. One of the ARVD patterns is Autosomal dominant and another is Autosomal recessive. 

Autosomal dominant: Autosomal dominant is one of the patterns of ARVD where one of the parents of an ARVD patient is also diagnosed as a patient of ARVD. It can be stated that the presence of ARVD within the family members generates 50% chances of inheritance. The early symptoms or the onset of ARVD may vary between the patient and its parents (Jahng et al. 2021). However, it can be stated that the influence of inheritance is dominant in this case due to the presence of this cardiovascular disease in one of the parent genes. In this form of ARVD pattern, it can be also stated that this disease is prevalent in terms of different Geographic locations. 

Autosomal recessive: The autosomal recessive pattern of ARVD can also be considered as one of the forms of Naxos disease. The symptom of ARVD that has been mentioned earlier is also the same for this autosomal recessive pattern. As per the findings of Yesudian et al. (2020), Naxos disease can be characterised as the process of thickening the skin layer on feet soles and hand palms. It is also observed that this pattern of ARVD also causes wool-like hair structure which is extremely thick due to the presence of hyperkeratosis. 

It can be stated that the overall diagnosis, physical exam, family history along with the medical tests of the patients helps in understanding identifying the actual pattern of ARVD in order to provide effective treatment accordingly. 

2.3 Potential strategies for detecting the disease 

It has been mentioned that the detection and diagnosis of ARVD is complex which is why the mortality rate among healthy individuals is increasing. Some of the potential strategies that are utilised in order to detect this cardiovascular disease are explained below. 

Electrocardiogram: This is one of the common forms of strategies for detecting ARVD which represents the “S-wave upstroke > 55ms” along with an inverted T-wave. As per the explanations of Marcinkevics et al. (2018), more than 90% of the ARVD was organised through the abnormality and disrupted ECG reports. The right bundle fibres of the human heart I diagnosed with intrinsic abnormality through image evaluation of electrocardiogram. 

Figure 1: Epsilon wave of ARVD

(Source: Marcinkevics et al. 2018)

Signal averaged electrocardiogram: The signal average cardiogram is focused on three different criteria which includes “low amplitude signal”, “filtered QRS duration” and “root mean square” of last 40 ms amplitude (Gatzoulis et al. 2021). The Epsilon wave, T-wave along with abnormal SAECG plays a significant role in understanding the distorted dilation and contraction of the right ventricle due to ARVD. 

Figure 2: ECG Findings 

(Source: Gatzoulis et al. 2021)

Echocardiography: Echocardiography helps in revealing the abnormality in right ventricle structure which includes aneurysm formation, dilation, hypokinetic failure, septal motions along with tricuspid regurgitation.  

Cardiovascular magnetic resonance: This is another commonly used strategy of diagnosing ARVC which helps in analysing dysfunction, ventricular dilation, and aneurysmatic fibrosis and intramyocardial fat. As mentioned by Shen et al. (2019), the Diagnostic accuracy of CMR is based on sensitivity, PPV, NPV and specificity. 

Figure 3: Diagnostic accuracy 

(Source: Shen et al. 2019)

Right ventricular angiography: This is one of the major criteria that help in understanding the presence of right ventricular akinesis, aneurysm or dyskinesis. It can be stated that this and Geographic test is observer-dependent as well as a subjective diagnosis strategy. 

Right ventricular biopsy: This is one of the specific detection techniques of ARVD however, it lacks sensitivity due to the non-uniform filtration of fibro fatty (Gasperetti et al. 2021). This is one of the unusual strategies of detecting this cardiovascular disease. This strategy helps in understanding the walls of the right ventricular to analyse the presence of fibre and fat. 

Figure 4:  Right ventricular biopsy

(Source: Gasperetti et al. 2021)

2.4 Pharmacological and Non-pharmacological treatment of ARVD

ARVD can be identified as a clinical condition associated with the poor heart condition in individuals of comparatively younger age. As stated by Mattesi et al. (2020), the patients of ARVD can be both symptomatic and asymptomatic in nature. The treatment strategy of the individuals can therefore vary considerably based on their clinical presentation, risk stratification and the preference of the patients. The primary aim of the treatment procedure is to try and prevent the occurrence of serious events as effectively as possible that further requires the identification of the high risk patients in terms of the disease. Despite various researchers and clinical diagnosis processes, a larger progression of both pharmacological and non-pharmacological treatments of the disease has not yet been achieved.

The concept of pharmacological therapy generally tends to include some of the “Antiarrhythmic medications” for the purpose of symptomatic control in the patients. The drugs potentially provided to the patients are further known to include a combination of ‘beta-blockers’ and ‘amiodarone’ (Pubmed.ncbi.nlm.nih.gov, 2021). They are known to provide an advantageous impact over the suppression of the non-sustained “Ventricular Tachycardia” (VT), thereby reducing the frequency of the ventricular arrhythmias. Moreover, Sotalol and Amiodarone have also been proposed as medications in the effective treatment of sustained VT and Ventricular Fibrillations (VF). The effectiveness of inducible and non-inducible VT is known to possess an efficacy rate of almost 68.4% and 82.8% respectively in the ARVD patients (Ncbi.nlm.nih.gov, 2021). On the contrary, the effectiveness of Amiodarone is much less, being just 15.4% and 25% for the inducible and non-inducible groups (Ncbi.nlm.nih.gov, 2021).

The non-pharmacological treatments are generally known to include the prophylactic implantation in the patients based on their clinical profiles. The Implantable Cardioverter Defibrillators (ICD) is also known to be one of the major factors associated with this particular treatment procedure. It has been further identified that the survival rates of the patients has been a whopping 96% in the patients with ICD compared to that of 72% in the patients without the implantation (Amjmedsci.com, 2021). Along with that, other therapeutic measures including the “Multicentre Automatic Defibrillator Implantation Trial Reduce Inappropriate Therapy” (MADIT-RIT) has also been incorporated in the patients undergoing the implantation procedure.

2.5 Literature Gap 

The overall literature understanding within this research report is based on the types, diagnosis and treatment of ARVD. Multiple patterns and dimensions have been incorporated within the discussion.  However, adequate contemporary data is lacking within this literature review which reduces the credibility and develops a knowledge gap.

Chapter 3: Methods

3.1 Research philosophy

Research philosophy is generally based on the nature and beliefs of the researchers associated with the conduction of the research process. The current research study is based on assessing and evaluating the disease Arrhythmogenic Right Ventricular Dysplasia, its types, genetics as well as the treatments associated with the medical condition. The research will further be based on the positivism research philosophy based on the effect hypothesis of the empirical study process. This particular philosophy will help in acquiring considerable knowledge regarding the disease condition and its associated factors.

3.2 Research approach

The research approach is further based on the different factors, plans and strategies associated with the approach of the research process. It is further based on gaining a knowledgeable insight in terms of the chosen topic (Woiceshyn and Daellenbach, 2018). In the particular study process, the inductive research approach will be selected as the primary one during the study process, it will further emphasise over the incorporation of different factors and processes associated with determining the inheritance factors of the Arrhythmogenic Right Ventricular Dysplasia. Collection of effective information via this particular method will also help the researchers regarding gaining appropriate data regarding the types of the disease patterns. The clinical symptoms of the disease, its potential cause and effects of the condition can thereby be selected based on the various types of research process.

3.3 Research design

Research design can be identified as the comprehensive framework that is often incorporated with the research process in terms of acquiring the issues faced by the individuals regarding the occurrence of the syndrome. This particular research method will emphasise over the utilisation of exploratory research design. As per the identification of Williams et al. (2020), the explanatory design tends to maintain the quality of the data by providing a sustainable emphasis towards the management of the collected data and information. The background of Arrhythmogenic Right Ventricular Dysplasia is collected by the researchers by the accurate incorporation of the exploratory research design within the research process.

3.4 Data collection tools and analysis

The accurate collection and analysis of the available information are considered to be an integral part of the research process. It is an already depicted fact that ARVD is a rarely occurring disease with symptomatic and asymptomatic features. It is further to be stated that the disease can be fatal especially in terms of the younger patients. In order to properly focus towards the research objectives and to save time and money, the researchers have decided to opt for the secondary data collection method. Furthermore, qualitative data will also be utilized for the appropriate collection of the available data and information. Hence, the gathering and analysis of the data will depend on the collection of appropriate journals, articles and other relevant sources. Therefore, relevant articles will be collected from the different online and offline sources based on the selection of the topics.

3.5 Timeline

Please refer to the appendix

3.6 Ethical considerations

The collection of the necessary data and information generally includes the maintenance of relevant ethical considerations based on the selected topic of ARVD. The collected data and information need to be reliable and authentic in nature. Necessary credits are to be provided to the authors by providing proper citations within the research work. Furthermore, the improvisation or tampering of the data and information need to be avoided as strictly as possible. Maintaining all the aforementioned aspects and factors will ensure the maintenance of necessary quality in terms of the research process.

Chapter 4: Results

There is various researches done on the topic of ARVD and they have paved the opportunity of acquiring relevant knowledge regarding the comprehensive understanding of the subject.

Various s researchers have showcased the evaluation and the impact of structural progression in the ARVD in the patients. The arrhythmic course within the disease has also been specifically assessed and evaluated in the current research process. As per the findings of Gandjbakhch et al. (2018), ARVD is denoted as an inherited cardiomyopathy that is clinically characterised by the ventricular dysfunction and the ventricular arrhythmias. The concept of ARVD is considered to possess various characteristic features associated with it. The progressive nature of the syndrome, however, is still less diagnosed than the others. The structural progression of cardiovascular disease can be assessed and evaluated by evaluating the clinical condition of the patients. It is further to be mentioned that the responses associated with the evaluation of structural progression underwent a routine “12-lead ECG Recording” at the baseline as well as the last follow-up (Mast et al. 2017). Furthermore, the genetic testing of the patients was also performed by the process of “Molecular Genetic Screening”. The genes included within the procedure constituted o plakophilin-2, desmocollin-2, OMIM, desmoplakin and plakoglobin. Furthermore, the non-desmosomal analysis of the patients was also carried out based on the “Transmembrane protein 43” (TMEM43). It was further identified that the ARVD is actually a progressive cardiomyopathy which is further marked by the “Interpatient variability” in the rate of the disease progression. The disease progressing characteristics of the syndrome is quite unique and thereby needs to be emphasised upon all the more for the effective determination of the assessed topic.

The therapeutic strategies of the disease are also to be taken into account for the sustainable mitigation of the issues faced by the onset of the disease. The disease of ARVD is characterised ventricular tachyarrhythmia, right ventricular dysfunction leading to a sudden cardiac arrest. It can be further stated that the mutation in the genes encoding the desmosomal protein are the most common and well known genetic basis of the disease. It is further to be stated that the common symptoms include syncope, palpitation and light-headedness. There are in fact certain aspects associated with the management of the ARVD. The establishment of an accurate diagnosis process includes the risk stratification for the sudden death and decision for an implantable cardioverter defibrillator. The most common type of ICD is the ones with single chambers. This type of ICD is also known to minimise the risk of long term complacent especially in case of the younger adults. The prevention of sustained ventricular arrhythmias and the prevention of progression and development of heart failures are the preliminary approaches that are to be taken into account for the sustainable decrease of the disease effectiveness. Another approach or strategy includes cardiac transplantation. Although heart transplant is rarely necessary in case of ARVD, it can be included as a last resort in case of the end stage heart failures and debilitating lethal arrhythmia. Patients majorly requiring heart transplant are of younger age. The comprehensive survival percentage of the patients affected with ARVD at 1 year, 5 years and 10 years of age are 87%, 81% and 77% respectively (Wang et al. 2019). Therefore, it can be stated that the percentage of survival in case of heart transplantation tends to be sustainably higher at a younger age. 

The disease of ARVD is a fatal condition often associated with sudden cardiac death (SCD) of the individuals. Various researches have thereby provided emphasis towards the initiation of a comparatively new prediction model associated with the minimisation and mitigation of the disease as effectively as possible. The development of the predicted model was based on the baseline characteristics of the patients both with and without the sustainability of the VA during their respective follow up procedure. The optimisation of the model is further calculated to be almost 0.77 which is almost 95% (Cadrin-Tourigny et al. 2019). Other than that the internal validation of the concept further provided an emphasis towards the fact that the calibration slope of the model was almost 0.93 thereby reflecting a smaller volume of over optimism. The clinical utility of the model is also known to explore and implicate its utilisation over the clinical practice and the comprehensive aspects that are to be taken into account for the sustainable development of the process in terms of ARVD. Along with that, the ventricular arrhythmia risk prevention model can further be taken into account with respect to the betterment of the clinical condition of the patients. It has been further identified that the models can be classified into two major types, namely the univariate model and the multivariate model. The greatest clinical utility and incorporation of the model lies within the fact that it is accurately capable of quantifying the arrhythmic risk of an individual. The model can classify the patients based on high, intermediate and low risk strata by treating the VA risk as a continuum. It is to be further stated that the risk of the model is actually there, however, the advantages and the benefits associated with the model ensures its utility within the clinical practice for detecting ARVD based on the requirement of the patients. 

Chapter 5: Discussion

Arrhythmogenic Right Ventricular Dysplasia is generally known to arise from different processes. The reason associated with the initiation of the clinical condition is generally known to be based upon the genetic factors. It is actually a rare inherited heart muscle disease that is characterised by Ventral Tachycardia and ventral tachyarrhythmia. There are in fact various strategies and processes associated with the right ventricular dysplasia. The accurate detection of the disease is further known to include various aspects based on which the disease can be accurately evaluated and assessed. The evaluation of the structural progression of ARVD is further considered to be an effective research process to be associated with the current research condition. It needs to be depicted that there are different aspects and factors associated with the progression of the disease which is to be further taken into account by the researchers for the effective mitigation of the disease process. The data and information characterising the structural progression is also to be stated. Other than that, the formation of a new progression model is also provided based on which the risk of the disease can be decreased up to a certain extent.

The above research is further known to provide sustainable understanding of the different types of ARVD. Furthermore, it can be stated that there are various aspects aligned with the disease. Various methods for the effective detection of the syndrome have further been evaluated along with the treatment procedures as well. From all the acquired information, it can be stated that ARVD is a quite fatal disease which otherwise can be controlled by implementing various plans and strategies. The involvement of genes within the occurrence of the disease is also required to be considered by the researchers for the successful mitigation of the disease.

Acknowledgement

I am extensively grateful towards the people who have helped me immensely during the completion of my research. I express my heartfelt gratitude to my professors who have showered continuously with their help and support.  I am also thankful to my fellow classmates who have supported me consistently during the project. It would have never been completed in time without their unconditional help and cooperation. Besides that, I would also like to thank my supervisor and my family members for their support.

References

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Appendix

Timeline (Gantt chart) 

Main activities and stages	Week 1	Week 2 to 8	Week 8 to 14	Week 14 to 19	Week 19 to 21	Week 21 to 23	Week 24
Selection of the topic
Collection of data
Planning the proper layout
Reviewing literature
Development of research plan
Selecting research technique
Gathering primary data
Data analysis
Interpretation of findings
Conclusion preparation
Project rough overdraft
Final submission