Interview with Prof. Gianluigi Condorelli, Director of the Humanitas Cardiovascular Department (Milan)
The rare heart and cardiovascular diseases include a wide range of conditions, each with its own peculiarities: from hypertrophic cardiomyopathy to Marfan syndrome o di Brugadapassing through pathologies such as cardiac amyloidosis, rare heart diseases can be pathologies in their own right or symptoms of other diseases. In all these diseases, the diagnostic and therapeutic approach requires a multidisciplinary team, which may include cardiologists, geneticists, ophthalmologists and other specialists, depending on the specific manifestations of the disease. Genetic diagnosis plays an increasingly important role, allowing for better understanding and management of these complex cardiac and cardiovascular conditions. We talked about it with Gianluigi Condorelli, Director of the Cardiovascular Department of the Humanitas hospital in Rozzano (MI).
FROM KAWASAKI DISEASE TO HYPERTROPHIC CARDIOMYOPATHY: A VAST AND SUBMERGED WORLD
Let’s try to make a quick overview of the most well-known rare cardiovascular diseases. They can affect only the heart muscle, or affect the cardiovascular system.
The hypertrophic cardiomyopathy It is the most common of rare heart diseases, with an incidence of approximately 1 in 500 people. The main characteristics are the autosomal dominant transmission (50% probability of transmission to children), the wide variability in the clinical manifestation (from asymptomatic to severe). The main symptoms are: arrhythmias (which can cause sudden death), symptoms from obstruction to the outflow of blood from the left ventricle (come dizziness e fainting), shortness of breath (dyspnea), fatigue, palpitations.
The malattia in Kawasaki it is a pathology that mainly affects children, causing inflammation of the coronary arteries. It is a form of arteritis with systemic manifestations, which distinguishes it from other cardiac pathologies. Among the symptoms we find: fever, redness of the conjunctiva, redness of the lips and the inside of the mouth, abnormalities of the extremities (hands, feet, diaper area), visible skin changes and enlarged lymph nodes in the neck on one side only.
The Marfan’s syndrome it is a collagen pathology that affects not only the cardiovascular system, but also the skeletal system. “People with this syndrome are often very tall – explains Condorelli – with walking problems and anomalies in their hands and feet. The main cardiovascular concern in these patients is the risk of rupture or dissection of the aorta, due to the fragility of the arterial tissue. Treatment focuses on blood pressure control and careful monitoring, with surgery when necessary.”
Moving on to heart rhythm pathologies, we have conditions such as long QT syndrome and Brugada syndrome. “These genetic disorders can lead to life-threatening arrhythmias. Management of these conditions may include the implantation of defibrillators in high-risk cases or the use of antiarrhythmic drugs in less severe situations. Family history of sudden death is an important factor to consider in the evaluation of these patients.”
The Takotsubo cardiomyopathy, instead, it is rare, but it is not genetic. It is a temporary condition often triggered by intense emotional stress, which causes temporary dilation of the heart. Fortunately, in most cases, it resolves spontaneously within a few weeks.
Cardiac amyloidosis, on the other hand, is one pathology characterized by the accumulation of abnormal proteins in the heart. “It can be secondary to systemic diseases such as multiple myeloma – recalls Condorelli – or linked to genetic mutations that cause the accumulation of the transthyretin protein. Recent advances in therapy include drugs that reduce the aggregation of these proteins or decrease their production, offering new hope for patients with this condition, especially if diagnosed early.”
Among the less frequent heart diseases we find pathologies such as hemochromatosis, characterized by excessive accumulation of iron in the body. Another interesting, although no longer as common, condition, or the rheumatic fever. This disease, once much more common, is linked to streptococcal infections in children. With the advent of antibiotics, its incidence has dramatically decreased over the last 30-50 years. Rheumatic fever could cause various complications, including myocarditis and valvular diseases such as mitral stenosis. Today it is rare to find people under 40 with this condition.
THE IMPORTANCE OF GENETIC DIAGNOSIS AND CORRECT THERAPIES
The identification of a genetic mutation associated with significant cardiovascular events (such as ventricular fibrillation or heart failure) is crucial to implement targeted prevention strategies, monitor the patient more carefully, and carry out family screening to identify other members at risk. “Genome sequencing technologies have made great strides in recent yearsmoving from basic research to clinical application. This progress has made identifying the genetic components of rare heart diseases more accessible and practical.”
The current approach involves three phases: targeted sequencing which analyzes a specific set of genes known to be associated with cardiac pathologies; the validation of mutations which occurs by comparing the genetic variants identified with existing databases, to verify whether they have already been associated with specific pathologies and the extended analysis, i.e. the sequencing of the entire exome to identify new mutations. It is important to note that only in approximately 40% of cases of dilated heart disease can a specific genetic component be identified. In the remaining cases, the pathology could be the result of other factors, such as previous heart inflammation.
In addition to genetic diagnosis, in the field of rare heart diseases, advanced imaging, particularly cardiac magnetic resonance imaging, offers a detailed view of the heart, complementing traditional echocardiography in screening and diagnosis.
On the therapeutic front, new drugs aim to improve cardiac relaxation, modulate contractility and control arrhythmias. These innovative treatments are combined with surgical interventions, which in cases such as obstruction of ventricular flow in hypertrophic cardiomyopathy, can restore almost normal cardiac function.
