Palpitations, tiredness, breathlessness, difficulty exercising or, more rarely, syncope, angina and dyspnoea. These are the symptoms of hypertrophic obstructive cardiomyopathy which affects over 100 thousand people in Italy of which, however, only about 15 thousand have received a correct diagnosis. In the remaining cases, the symptoms are confused with those of other heart diseases or are underestimated. This pathology, which causes the thickening of the heart muscle, in fact presents signs common to many other clinical conditions and can therefore be confused with different diseases, especially in young people. Today a virtual media tutorial, promoted by Bristol Myers Squibb, is dedicated to the pathology and new perspectives in treatment.
A genetic disease
Hypertrophic obstructive cardiomyopathy is a very common genetic disease: “The proteins of the heart are altered with an abnormal increase in their contractile activity”, he explains I receive Olivet, full professor of Cardiology at the University of Florence and Director of Pediatric Cardiology at the Meyer University Hospital (AOUM). The pathology causes an important thickening of the walls of the heart muscle and a disproportionate increase in energy consumption, which in the long term can also have very serious consequences”.
The most common symptoms are palpitations, tiredness, shortness of breath and difficulty exercising, especially after meals. “More rarely – adds Olivotto – syncope, angina and dyspnoea occur. In the so-called obstructive forms, there may also be an obstacle to the flow of blood from the left ventricle, which, in some cases, requires surgical correction. There are, however, even mild and completely asymptomatic cases. This makes the diagnosis even more complex, especially in young people”. The disease is typically diagnosed around age 40, but is often present as early as adolescence. “Sports medicine – continues the cardiologist – is able to recognize it in asymptomatic stages thanks to the tests required for athletes, especially the ECG, and is able to significantly reduce the cases of sudden deaths during sports competitions. This disease compromises the quality of life, because it can make even the simplest activities difficult. Very often this is the first sign that prompts patients to carry out a check-up with their doctor”.
The role of genetic testing
Hypertrophic cardiomyopathy is a hereditary disease determined by mutations in one of the genes that code for the proteins of the sarcomere, the functional contractile unit of cardiac muscle cells. It is the most frequent familial genetic cardiac disease, mostly transmitted in an autosomal dominant manner. “The genetic test – underlines Olivotto – is indicated for each patient, even if not all choose to carry it out. It is positive in about half of the cases and is useful for studying the other members of the family. In the remaining 50% of patients, the test is negative, which means that the disease could have developed on a polygenic basis.In the absence of a single responsible gene, only clinical screenings can be performed on family members, therefore with ECG, in adults about every 5 years, in adolescents more often, because by age they are at risk of developing the disease even if they are still asymptomatic. The test on family members allows you to identify who needs to be followed up over time. These are extremely sensitive tests, which today can be performed quickly, but are complex to interpret: for this reason it is very important to make use of a geneticist with specific experience in heart disease”.
Who to contact
In Italy there are several treatment centers with specific experience for this pathology and for other genetic heart diseases. “Since the 1990s, the culture relating to hypertrophic obstructive cardiomyopathy has spread very much, we are one of the countries able to treat it best – continues Olivotto. It is essential, however, that patients turn to dedicated centres, which have much more experience in recognizing symptoms, providing correct information and identifying the best treatment”.
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How to proceed for therapy
Surgery is recommended only for severe obstructive forms and requires hospitalization in centers of excellence, because it is a rare operation. “For many of these patients – explains the cardiologist – the implantation of a life-saving defibrillator is necessary. The majority of cases instead require drug therapy, which until now has consisted of beta-blockers, calcium channel blockers and antiarrhythmics, developed for other pathologies The first therapy specifically developed for hypertrophic cardiomyopathy, mavacamten, is a first-in-class oral allosteric modulator of cardiac myosin, whose clinical data validate its promising potential as an important treatment option for symptomatic patients with the obstructive form.” Mavacamten, already available in the US and pending registration in Europe, has shown important potential to provide rapid and long-lasting improvement of some key heart abnormalities in patients living with this chronic, sometimes progressive disease.
The results of clinical trials
In the EXPLORER-HCM study, mavacamten showed a considerable improvement in the Kansas City Cardiomyopathy Questionnaire (KCCQ OSS): 36% with mavacamten versus 15% with placebo. The KCCQ OSS is a 23-item disease-specific questionnaire that quantifies patients’ symptoms, physical condition, social function, and quality of life. This analysis supports the scientific evidence indicating the benefit of the drug in improving health conditions, symptoms and quality of life.
The EXPLORER-LTE study enrolled, at the end of the EXPLORER-HCM study, 231 of the 244 patients who were eligible for the long-term extension study. EXPLORER-LTE demonstrated sustained improvements in cardiovascular benefits at weeks 48 and 84 and the potential for mavacamten to provide rapid and sustained improvement in key cardiac measures.
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82% of patients did not need septal reduction
The VALOR-HCM study also found that the addition of mavacamten significantly reduces the need for septal reduction procedures (SRT) in patients with severe symptomatic hypertrophic obstructive cardiomyopathy who are candidates for SRT, according to the 2011 American College Guidelines of Cardiology/American Heart Association (ACC/AHA). Of patients treated with mavacamten, 82% no longer needed SRT and no longer met guideline criteria for SRT compared with 23% of patients who received placebo. Patients treated with mavacamten also demonstrated improvement in measures of quality of life and cardiac biomarkers. Surgery and pharmacological therapy, useful for treating the disease when it has already occurred, are joined by the first initiatives of gene therapy, for a pre-clinical intervention. “The goal is to replace or repair the gene that presents the alteration in a very early stage of the disease, to eliminate it completely – concludes Olivotto. It will be aimed at young patients, but research is still in progress”.