Patient web survey
A total of 3089 adult patients were invited to complete the survey, with 2469 surveys successfully delivered. Of these, 474 responses to the survey were received, of which 444 responses (94%) were complete, self-reported an HCM diagnosis, and were analyzed. Among all respondents, 58.0% reported a diagnosis of oHCM (i.e. “have you been diagnosed with left ventricular outflow tract obstruction?”), 33.1% reported a diagnosis of nHCM, and 8.8% did not know their specific HCM condition. Overall, fatigue (74%), shortness of breath upon exertion (73%), and light-headedness (70%) were reported as the symptoms experienced most often. Other symptoms reported by more than half the respondents included palpitations (54%), dizziness after exertion (54%), and exercise intolerance (57%). Chest pain was reported by 39% of respondents and fainting by 24%.
When asked about the impact of their symptoms on physical activity, 21% reported no limitation, 42% reported slight limitation, 31% reported marked limitation, and 6% reported being unable to be physically active without discomfort.
Patients with oHCM reported experiencing a greater number of symptoms than did patients with nHCM: 84% of oHCM patients reported experiencing four or more symptoms characteristic of HCM, versus 55% of nHCM patients. When asked to define the severity of their symptoms using descriptions based on the NYHA functional classification scale, 43% of patients with oHCM reported moderate-to-severe symptoms (i.e. NYHA Class III or IV), compared with 27% of nHCM patients. About 70% of patients with oHCM reported that their symptoms had somewhat or significantly worsened since their diagnosis, and that their symptoms had a greater impact on their ability to work.
The time between first experiencing symptoms and being diagnosed with HCM was reported as < 3 months by 36.5% of respondents, 3 months to 1 year by 14.1%, 1–3 years by 11.2%, 3–5 years by 6.6%, and > 5 years by 18.7%; 12.9% of respondents reported having never experienced symptoms.
Literature review
The literature search yielded a total of 256 abstracts and titles for potential consideration. A total of 220 studies were excluded; the main reasons for exclusion were irrelevant patient population or no mention of PROs, symptoms, or impacts. After full-text review of the remaining 36 articles, 28 studies were excluded; the main reason for exclusion was no mention of PROs. The final set of eight articles included for review comprised five cross-sectional studies, one qualitative study, one cohort study, and one cost-effectiveness study.
The articles describing the experiences of patients with HCM identified in the literature review revealed shortness of breath or dyspnea, chest pain (angina) (30, 31), and syncope (30–32) to be the primary complaints/symptoms of patients with HCM.
Similarly, all three HCM professional guideline documents describe patients with HCM as having common symptoms of dyspnea, palpitations, chest pain (angina), and syncope (1, 3, 4). Furthermore, the literature review identified fatigue (4), tachyarrhythmia (31, 32), orthopnea (9), pulmonary congestion (1), excessive sweating (4), and heart failure (4, 32) as additional symptoms experienced by some patients with HCM.
The patient advocacy websites also indicated that symptoms such as chest pain, light-headedness, blackouts/dizziness, and fatigue were common in HCM (28, 29). In addition, the websites noted arrhythmia, cardiac arrest, and endocarditis as other symptoms experienced by some patients with HCM (28, 29).
These symptoms identified by the literature review were considered highly impactful on the mental health, physical functioning, and overall quality of life of patients (16, 18, 31–34). Depression was also commonly reported in several studies (32, 33) and on the patient advocacy websites (28, 29). The most commonly reported impact measured in the literature review was anxiety, which was mentioned in four studies (32–34). It was also noted on the patient advocacy websites (28, 29).
Overall, the review was consistent in identifying shortness of breath/dyspnea, light-headedness and blackouts/syncope, palpitations/tachycardia, fatigue, and dizziness as the most common symptoms among patients with HCM. Furthermore, anxiety, depression, and reduced physical functioning with shortness of breath were identified as being particularly impactful on patient quality of life and functioning.
Although the presence of left ventricular outflow tract obstruction (oHCM) was associated with more severe symptoms and greater risk of heart failure and cardiovascular death (2), there was limited information in the literature describing differences in symptom experiences between patients with oHCM and those with nHCM. This topic was explored further in the clinician and patient interviews.
Clinical expert interviews
The clinical expert interviews showed the three clinicians to be highly consistent in their views of the symptom burden of HCM and how these symptoms impact patients’ lives. They reported that symptoms are experienced by most patients diagnosed with HCM, particularly those with oHCM, and that the most commonly reported symptoms were shortness of breath with exertion or after a meal, chest pain (angina), palpitations, and syncope/feeling faint or dizzy. The three clinical experts reported that the symptoms of HCM are often nonspecific, overlap with one another, can vary from day to day, and can show similarities with side effects of treatment or symptoms of a comorbidity. Because of these challenges, they said that symptoms alone are rarely used to diagnose HCM in their practices, and physical and imaging assessments are required.
When asked to what extent the most frequently reported symptoms were consistent with their assessment of the cardinal symptoms of HCM, all clinicians referred to the difficulty in untangling the symptoms of HCM from treatment side effects or comorbid issues such as obesity. For example, fatigue, hypertension, and sexual impairment were listed as symptoms that could be due to treatment, and shortness of breath was listed as a symptom that could also be due to excess weight.
Of these commonly experienced symptoms, shortness of breath and dizziness/light-headedness were considered by two of the three clinical experts as the most bothersome to patients. Chest pain (angina), feeling faint (syncope), tiredness/fatigue, and palpitations were also ranked by one of the three clinical experts as among the most bothersome for patients. Exertion was considered to be the predominant trigger for symptoms (with the exception of chest pain [angina], which can occur spontaneously). Limitations to physical activity were considered to have the greatest impact on patients’ lives, and the clinicians reported that many patients avoid exercise out of fear of sudden death. The experts cited anxiety as the most common psychological impact related to patients’ HCM symptom burden.
The clinicians were asked to describe how the experience of patients with oHCM and nHCM are similar or different, and their responses are summarized in Table 1. The clinicians reported that, in general, patients with oHCM experience very similar symptoms to patients with nHCM, but patients with oHCM may experience more symptoms simultaneously, more severe symptoms, and more consistent and sustained symptoms than do patients with nHCM.
Table 1
Clinical similarities and differences between oHCM and nHCM as reported by clinical experts
Are there differences between oHCM and nHCM with regard to: | Clinician 1 (Italy) | Clinician 2 (US) | Clinician 3 (France) |
Number of symptoms? | • Obstructive patients have more reproducible and constant symptoms | • Obstructive patients have more symptoms | • (Clinician did not provide answer to this question directly) |
Types of symptoms? | • Obstructive patients experience palpitations and syncope after effort (recovery phase); not as typical for nonobstructive patients • Syncope on effort is rare, and a worrying sign of severity and instability | • Obstructive patients experience more light-headedness | • Obstructive patients have more frequent shortness of breath with exercise, dyspnea, and angina • Dizziness and palpitations are also more likely with obstruction |
Severity of symptoms? | • Obstructive patients experience more severe symptoms | • Obstructive patients perhaps experience more severe symptoms • Symptoms show up earlier in the disease course so they progress more than in nonobstructive patients | • More severe with obstruction |
Frequency of symptoms? | • Patients with oHCM have more frequent and reproducible symptoms than those with nHCM • Non-obstructed patients are much more variable and difficult to reproduce symptoms in | • Not really; once symptoms show up, they are there | • More frequent with obstruction |
Impacts of symptoms? | • Obstructive patients have more symptoms, more severe symptoms, and are more consistently symptomatic • When someone nonobstructive gets progressive symptoms, this is harder to deal with because it is harder to treat | • Patients with more symptoms and those more functionally disabled tend to be more depressed, so perhaps a greater proportion of patients with obstructive disease are depressed because they tend to have more severe symptoms earlier in the disease | • Symptoms are nonspecific so you must rely on more solid parameters (degree of thickness and obstruction, fibrosis, and arrhythmias), but because obstruction can lead to more severe symptoms, it can lead to more impacts |
Psychological impact of HCM? | • All clinicians stated that there were psychological impacts associated with HCM and that it was most common for patients to have anxiety, especially after the initial diagnosis • Generally, the clinicians thought that obstructive patients experienced a greater psychological impact as a result of the greater severity of their symptoms compared with nonobstructive patients • Overall, clinicians perceived the patients with the most severe symptoms as more likely to experience a psychological impact |
HCM hypertrophic cardiomyopathy; nHCM nonobstructive HCM; oHCM obstructive HCM; US United States of America |
Patient concept elicitation interviews
Concept elicitation interviews were performed with a total of 27 patients with HCM. Demographic and clinical information for the 27 interviewed patients is summarized in Table 2. The mean age of the patients was 44.6 years, and the most common comorbid conditions were anxiety (40.7%), hypertension (29.6%), and depression (25.9%). Patients rated the severity of their HCM symptoms that day as very mild (15.4%), mild (30.8%), moderate (46.2%), severe (3.8%), or very severe (3.8%). Clinical confirmation of obstructive status was missing for seven patients; four of these patients self-reported oHCM diagnoses, and self-reported obstructive status was unknown/missing for three patients.
Table 2
Demographic and clinical characteristics of concept elicitation patient interviewees
Characteristic | Patients (N = 27) |
Sex, male, n (%) | 11 (40.7) |
Age, yrs, mean (SD) [range] | 44.6 (15.01) [22–74] |
Age first diagnosed with HCM, yrs, mean (SD); median [range] | 32.2 (17.11); 27 [0–72] |
Country, n (%) |
UK | 8 (38.1) |
France | 6 (22.2) |
Italy | 7 (25.9) |
US | 6 (22.2) |
Employment status, n (%) (patient-reported) |
Employed, full-time | 12 (44.4) |
Employed, part-time | 5 (18.5) |
Homemaker | 1 (3.7) |
Student | 1 (3.7) |
Retired | 5 (18.5) |
Disabled | 1 (3.7) |
Othera | 2 (7.4) |
Is HCM the subject’s primary cardiovascular diagnosis? (clinician-reported) |
Yes, n (%) | 22 (81.5) |
How long has the subject been diagnosed with HCM? (clinician-reported) |
Yrs, mean (SD) | 9.3 (8.24) |
HCM obstruction status, n (% ) (clinician- or patient-reported)b |
Obstructiveb | 11 (40.7) |
Nonobstructive | 13 (48.1) |
Missing | 3 (11.1) |
Health conditions, n (%)c (patient-reported) |
None | 7 (25.9) |
Anemia | 5 (18.5) |
Angina | 5 (18.5) |
Anxiety | 11 (40.7) |
Arthritis | 2 (7.4) |
Cancer | 2 (7.4) |
COPD/emphysema | 1 (3.7) |
Depression | 7 (25.9) |
Diabetes | 1 (3.7) |
Hypertension | 8 (29.6) |
Myocardial infarction | 2 (7.4) |
Atrial fibrillation | 5 (18.5) |
Severity of HCM symptoms as rated “today”, n (%) (patient-reported) |
Very mild | 4 (15.4) |
Mild | 8 (30.8) |
Moderate | 12 (46.2) |
Severe | 1 (3.8) |
Very severe | 1 (3.8) |
Overall health, n (%) (patient-reported) |
Excellent | 2 (7.4) |
Very good | 2 (7.4) |
Good | 17 (63.0) |
Fair | 5 (18.5) |
Poor | 1 (3.7) |
COPD chronic obstructive pulmonary disease; HCM hypertrophic cardiomyopathy; SD standard deviation; UK United Kingdom; US United States; yrs years |
aOther included self-employed/PhD student, and craftsman |
bObstructive HCM was clinician-confirmed for seven patients and self-reported by four additional patients; all 11 were considered to have obstructive HCM for the qualitative analyses |
cNot mutually exclusive |
Table 3 summarizes the frequency of HCM symptoms reported by interview participants. A total of 29 different symptoms were reported and complete content saturation was reached after 23 interviews. The most commonly reported symptoms included tiredness (89%), shortness of breath (89%), shortness of breath with physical activity (89%), and dizziness/light-headedness (89%). Other symptoms commonly reported included chest pain (angina) (70%), chest pain (angina) with physical exertion (70%), and palpitations (fluttering or rapid heartbeat) (81%).
Table 3
Frequency of HCM symptoms reported by at least two patients in concept elicitation patient interviews
HCM symptom | Patients (N = 27) n (%) |
Shortness of breath (dyspnea) | 24 (89) |
Shortness of breath when lying flat or at rest | 14 (52) |
Shortness of breath after meals | 15 (56) |
Shortness of breath with physical activity | 24 (89) |
Tiredness | 24 (89) |
Chest discomfort | 11 (41) |
Chest pain (angina) | 19 (70) |
Chest pain with physical activity/exertion | 19 (70) |
Chest pain after meals | 9 (33) |
Dizzy/light-headed | 24 (89) |
Fainting | 11 (41) |
Palpitations/heart beating quickly/heart fluttering/extrasystole/tachycardia | 22 (81) |
Sweating | 2 (7) |
“Couldn’t stand very well” (trouble standing) | 2 (7) |
Low heart rate | 2 (7) |
Overheating | 2 (7) |
Nausea | 5 (19) |
Headaches | 2 (7) |
HCM hypertrophic cardiomyopathy |
Participants with oHCM reported all the same major symptoms as those with nHCM. Among the oHCM participants, 20 symptoms were reported, of which 85% were reported in the first four interviews. Complete concept saturation in this sample was reached after nine interviews. Among the nHCM participants, 24 symptoms were reported; 88% of these were reported in the first 10 interviews. Concept saturation in this sample was reached after 13 interviews. The mean (standard deviation) number of symptoms reported did not vary between the two patient groups, with oHCM patients having 10.0 (1.76) versus nHCM patients having 8.8 (2.68, p = 0.24).
Table 4 lists the symptoms identified as most important to patients. The question was intentionally left open-ended for participants to consider factors that they deem important. Shortness of breath (81% overall; 91% oHCM; 69% nHCM) was the symptom most commonly reported as important, followed by tiredness (67% overall; 55% oHCM; 85% nHCM), palpitations (67% overall; 73% oHCM; 62% nHCM), and chest pain (56% overall; 64% oHCM; 46% nHCM). Two participants (10%) did not rate the importance of their symptoms.
Table 4
Symptoms identified as most important to patients during the concept elicitation interviews
HCM symptom, n (%) | Patients (N = 27)a |
Shortness of breath (dyspnea) | 22 (81) |
Tiredness | 18 (67) |
Palpitations/heart beating quickly/heart fluttering/extrasystole/tachycardia | 18 (67) |
Chest pain (angina) | 15 (56) |
Dizzy/light-headed | 13 (48) |
Fainting | 3 (11) |
Shortness of breath after meals | 2 (7) |
Shortness of breath with physical activity | 2 (7) |
Chest discomfort | 2 (7) |
Nausea | 2 (7) |
Chest pain after meals | 1 (4) |
Sweating | 1 (4) |
Overheating | 1 (4) |
Feet swelling | 1 (4) |
HCM hypertrophic cardiomyopathy; nHCM nonobstructive HCM |
aTwo nHCM patients did not provide a list of symptoms; the obstruction status of three patients was unknown |
Table 5 describes impacts of the disease on aspects of the patients’ lives identified during the concept elicitation interviews. A total of 15 impact concepts were identified. Concept saturation was achieved within the first 23 interviews. The most commonly reported impacts included limitations to physical activities (78%), emotional impacts (78%), feeling anxious or depressed (78%), and impacts on work (63%).
Table 5
Impacts of the disease most frequently identified by patients during the concept elicitation interviews
Impact of HCM, n (%) | Patients (N = 27) |
Limitations to physical activities | 21 (78) |
Emotional impacts | 21 (78) |
Feeling anxious or depressed | 21 (78) |
Work | 17 (63) |
Family | 16 (59) |
Social life | 16 (59) |
Limitations to daily tasks | 14 (52) |
Household chores | 13 (48) |
Sleep disruption | 12 (44) |
Driving | 1 (4) |
Communication | 1 (4) |
Can't get plastic surgery | 1 (4) |
Traveling | 1 (4) |
Needs to have recovery time after activities | 1 (4) |
Can’t take certain cold medicines | 1 (4) |
HCM hypertrophic cardiomyopathy |
Conceptual model development
The HCM symptoms reported by patient interview participants were largely consistent with the findings from the patient web survey, the literature review, and the interviews with the expert clinicians. The patient interviews provided additional specifics on the frequency and importance of these symptoms, and the impact they have on patients’ lives.
A conceptual model that organizes and prioritizes the most relevant concepts (both symptoms and impacts) in the HCM patient population was developed (Fig. 1). The conceptual model identifies shortness of breath, palpitations, fatigue/tiredness, dizziness/light-headedness, and chest pain as the core symptoms of both oHCM and nHCM. These symptoms have physical, emotional, and social impacts on patients, including limitations on their activities of daily living.