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Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study
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,* and Baptiste du Reau de la Gaignonnière, Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Project administration, Software, Supervision, Validation, Writing – review & editing#
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Abstract
Background
In 2019, 600’000 people in Africa died of heart failure and heart diseases will increase on the continent. It is crucial to understand the regional etiologies and risk factors for heart failure and underlying heart diseases. However, echocardiography data from rural Africa are scarce and from Lesotho non-existent. This study aims to examine the occurrence, characteristics and etiology of heart failure and heart diseases using echocardiography data from a referral hospital in rural Lesotho.
Methods
We conducted a retrospective cohort study at Seboche Mission Hospital, the only referral hospital in Butha-Buthe district (Lesotho) with an echocardiography department. We included data from all individuals referred to the department between January 2020 and May 2021. From non-hospitalized patients echocardiographic diagnosis, sex and age were available, from hospitalized patients additional sociodemographic and clinical data could be extracted.
Results
In the study period, a total of 352 echocardiograms were conducted; 213 had abnormal findings (among them 3 children). The majority of adult participants (130/210; 64%) were female and most frequent heart diseases were hypertensive (62/210, 30%), valvular (39/210, 19%) and chronic pulmonary (37/210, 18%). Heart failure represented 11% of hospitalizations in the same period. Among the 126 hospitalized heart failure patients, the most common etiology was chronic pulmonary heart disease (32/126; 25%). Former mine workers and people with a history of tuberculosis were more likely to have a chronic pulmonary heart disease.
Conclusions
The leading cause of heart disease in this setting is hypertension. However, in contrast to other African epidemiological studies, chronic pulmonary heart disease is unexpectedly common. There is an urgent need to improve awareness and knowledge about lung diseases, make diagnostic and therapeutic options available and increase prevention.
Introduction
During the last two decades, cardiovascular diseases have rapidly emerged as a major cause of disease and death in Africa [1]. According to the World Health Organization, cardiovascular diseases are among the top five causes of death in Africa. Almost 1.1 million people died because of cardiovascular diseases in Africa in 2019 [2]. Ischemic heart disease, stroke, and hypertensive heart diseases are identified as the three most common causes of cardiovascular death in Sub-Saharan Africa (SSA) [2].
The heart failure syndrome has been recognized as a significant contributor to cardiovascular disease burden in SSA for many decades. The increasing burden of heart failure in the region is driven by increasing urbanization, changes in lifestyle habits (decreased physical activity, increased alcohol and nicotine use), and ageing of the population, and thus, in a surge of hypertension, type 2 diabetes mellitus, dyslipidemia and obesity [3]. Mortality of patients with heart failure has been reported to be highest in Africa, compared to other low-and middle-income regions; in Africa alone the mortality of patients with heart failure was estimated at 34% [4]. The most commonly reported etiology of heart failure in low-and middle-income regions is ischemic heart disease, except for South America and Africa [5]. A recent meta-analysis from Africa including 10,098 patients from 22 studies found not ischemic/coronary heart disease but hypertensive heart disease to be the commonest cause of heart failure at 39.2%, followed by cardiomyopathies (21.4%), rheumatic heart disease (14.1%), and ischemic/coronary heart disease only at 7.2% [6]. However, data from low- and middle-income countries are scarce due to the non-availability of routine echocardiography, especially in rural areas.
The WHO estimates that cardiovascular diseases represent 14% of premature deaths due to non-communicable diseases in Lesotho [7]. Detailed data on heart diseases and heart failure in Lesotho, however, are non-existent. In this study, we describe the occurrence, characteristics, and etiology of heart diseases and heart failure, diagnosed using echocardiography, in patients from a rural referral hospital in Lesotho.
Methods
Study design
We conducted a retrospective cohort study at Seboche Mission Hospital. The secondary-level referral hospital is situated in Butha-Buthe district, Northern Lesotho, on 1800 meters above sea level. It is a public missionary hospital and serves a rural local population (Basotho), mostly subsistence farmers and migration workers. Since 2020, the hospital has an established echocardiography department that performs about 20–30 echocardiographic assessments (including electrocardiograms) per month and represents the only echocardiographic referral point for the entire district.
We included retrospective data of all individuals–children <18 years old and adults–referred to the echocardiography department between January 2020 and May 2021 due to signs and symptoms of heart failure. From patients that were hospitalized detailed sociodemographic and clinical data was available, whereas for the others only sex and age.
Data collection
We extracted data from in-patient routine medical records, the echocardiography department patient register and the echocardiography reports. The participants’ demographics, clinical information, echocardiography findings and laboratory values were entered into an electronic data capture spreadsheet by the physician and echocardiographer. Missing demographic information was collected through telephonic consultation with the patient. The data was double-checked by an external collaborator.
Definitions
We provide detailed information about the echocardiography machine, techniques and measurements used in S1 Text. We adhered to the following clinical and echocardiographic definitions:
Heart failure
Clinical syndrome of effort intolerance related to an abnormality of cardiac function, characterized by typical symptoms of shortness of breath, fatigue and leg swelling and accompanied by clinical signs of congestion, such as peripheral oedema, elevated jugular venous pressure and pulmonary crepitations [8].
Functional heart failure
Heart failure signs without cardiac abnormality, caused by another reason (e.g. severe anemia, hyperthyroidism).
Right heart failure
Tricuspid Annular Plan Systolic Excursion < 17 mm or RV systolic excursion velocity by tissue doppler imaging < 9.5 cm/s or fractional area change < 32% [9].
Hypertensive heart disease
Left ventricular (LV) hypertrophy or concentric remodeling (normal LV mass with a relative wall thickness > 0.42) with or without global systolic or diastolic left ventricular dysfunction in a patient with arterial hypertension (systolic blood pressure >140mmHg or diastolic blood pressure >90mmHg or presence of antihypertensive therapy), with neither valve disease nor segmental wall motion abnormalities [8].
Hypertrophic cardiomyopathy
A maximal end-diastolic wall thickness of ≥15 mm anywhere in the LV, in the absence of another cause of hypertrophy [10].
Hypertrophy of the LV in children
LV mass/height2.7 above the 95th percentile; severe LV hypertrophy: LV mass of at least 30% above the 95th percentile [11].
Dilated cardiomyopathy
LV or biventricular dilation and impaired contraction, not explained by abnormal loading conditions (e.g. hypertension and valvular heart disease) or coronary artery disease [12].
Valvular heart disease
Abnormal size and/or function of the heart and a primary abnormality of a valve (i.e., presence of valve regurgitation or stenosis and thickening of cusps, leaflets, or leaflet tips, vegetations or ruptured chordae tendineae). As a subgroup of the valvular heart diseases, rheumatic heart disease was defined according to the 2012 world heart federation criteria [13].
Coronary heart disease
Typical angina pectoris and ventricular dysfunction with segmental hypo- or akinesia which could be attributed to a specific coronary artery with or without typical ECG findings [8].
Pulmonary heart disease
Right heart failure in presence of pulmonary hypertension and normal left atrium pressure, sub-divided into either chronic or acute pulmonary heart disease [8].
Pericardial heart disease
Pericardial effusion as the primary reason for the heart failure. Tuberculosis (TB) pericarditis if clinically suspected or microbiologically confirmed TB [8].
Rhythmic heart disease
Congestive heart failure caused by rhythmic abnormalities (i.e., fast atrial fibrillation, complete auriculo-ventricular block) [8].
Congenital heart disease
Definition according to the American Society of Echocardiography Pediatric and Congenital Heart Disease Council [14].
Peri-/Post-partum cardiomyopathy
Cardiomyopathy with a reduced left ventricular ejection fraction (LVEF) of <45%, presenting towards the end of the pregnancy or in the months after delivery in a woman without previously known structural heart disease [15].
Statistical analysis
We used absolute and relative frequencies to describe categorical data and medians and interquartile ranges for continuous variables. Inferential statistical testing to investigate factors predicting the most common etiology of heart failure was conducted using univariate and multivariate logistic regression models. We applied two-sided p-values with alpha 0.05 level of significance and presented the results as odds ratios with 95% confidence intervals. Descriptive statistics were conducted using Microsoft Excel and inferential statistics using Stata (version 14, Stata Corporation, Austin/Texas, USA).
Ethics statement
The National Health Research and Ethics Committee of the Ministry of Health of Lesotho reviewed the study protocol and concluded that no written informed consent is needed since this is a retrospective study only involving the collection of existing data, registers and documents (ID146-2021; August 06, 2021).
Results
Between January 2020 and May 2021, a total of 352 echocardiograms were conducted at the echocardiography department of Seboche Mission Hospital. Of the 352 echocardiograms, 11 (3%) were follow-up assessments. Among the 341 included echocardiograms (335 adults and 6 children), 128 (38%) indicated normal or non-significant findings, e.g. a minimal mitral valve regurgitation without any other sign of a heart disease (Table 1).
Table 1
| Adults (n = 335) | |||
| Total (N = 335) | Abnormal echocardiogram (n = 210) | Normal echocardiogram (n = 125) | |
| Sex | |||
| female | 221 (66%) | 130 (62%) | 91 (73%) |
| male | 114 (34%) | 80 (38%) | 34 (27%) |
| Age, median (IQR) | 58 (46–72) | 62 (52–75) | 50 (33–65) |
| Only Adults with Abnormal Echocardiogram, by sex (n = 210) | |||
| Total (N = 210) | Women (n = 130) | Men (n = 80) | |
| Hypertensive HD | 62 (30%) | 48 (37%) | 14 (18%) |
| Valvular HD | 39 (19%) | 28 (22%) | 11 (14%) |
| Chronic pulmonary HD | 37 (18%) | 7 (5%) | 30 (38%) |
| Dilated CM | 26 (12%) | 17 (13%) | 9 (11%) |
| Coronary HD | 17 (8%) | 11 (8%) | 6 (8%) |
| Acute pulmonary HD | 9 (4%) | 6 (5%) | 3 (4%) |
| Pericardial HD | 9 (4%) | 6 (5%) | 3 (4%) |
| Rhythmic HD | 8 (4%) | 4 (3%) | 4 (5%) |
| Hypertrophic CM | 2 (1%) | 2 (2%) | 0 (0%) |
| Unclassified CM | 1 (0%) | 1 (1%) | 0 (0%) |
| Children (n = 6) | |||
| Total (N = 6) | Abnormal echocardiogram (n = 3) [1] | Normal echocardiogram (n = 3) | |
| Sex | |||
| female | 3 (50%) | 2 (67%) | 1 (33%) |
| male | 3 (50%) | 1 (33%) | 2 (67%) |
| Age, median (IQR) | 1 (1–2) | 2 (1–12) | 1 (1–1) |
Abbreviations: IQR (interquartile range), CM (cardiomyopathy), HD (heart disease)
[1] Congenital heart diseases: 1 girl with an aortic stenosis (bicuspid aortic valve) and 1 girl and 1 boy with a patent ductus arteriosus
Heart diseases: Occurrence, characteristics and etiology
Among the 213 individuals with abnormal findings, 3 were children (all with a congenital heart disease), and the remaining 210 participants were adults, of whom the majority (130/210; 64%) were female and were a median age of 62 (interquartile range [IQR] 52–75) years old (Table 1). The most frequent heart diseases among adults were hypertensive (62/210, 30%), valvular (39/210, 19%), chronic pulmonary (37/210, 18%), dilated cardiomyopathy (26/210, 12%), and coronary heart disease (17/210, 8%), followed by the remaining etiologies below 5% prevalence (Table 1 and Fig 1).
Heart failure: Occurrence, characteristics and etiology
Among the 210 adult individuals with abnormal findings, 118 were hospitalized due to heart failure. In the same time period, in addition, eight adult patients with functional heart failure, i.e. caused by another reason than cardiac abnormality (e.g. severe anemia), were hospitalized. Overall, at Seboche Mission hospital between January 2020 and Mai 2021, hospitalization due to heart failure represented 11% (126/1164) of all hospitalized patients. The majority of patients hospitalized due to heart failure were female (56%; 70/126) and had a median age of 66 years old (IQR 54–76). 61% (77/126) had arterial hypertension, 65% (82/126) took cardiac medication at presentation, 20% (25/126) were diabetic, 13% (17/126) lived with HIV and 15% (19/126) had a history of tuberculosis. A total of 14% (18/126) were smokers and 23% (29/126) former mine workers. During clinical examination, most presented with oedema (94%; 118/126) and dyspnea (91%; 115/126) (Table 2).
Table 2
| Total (n = 126) | Male (n = 56; 44%) | Female (n = 70; 56%) | |
|---|---|---|---|
| Characteristics and cardiovascular risk factors | |||
| Age in years, median (IQR) | 66 (54–76) | 68 (56–76) | 66 (51–75) |
| Hypertensive | 77 (61%) | 20 (36%) | 57 (81%) |
| Diabetic | 25 (20%) | 6 (11%) | 19 (27%) |
| Living with HIV | 17 (13%) | 9 (16%) | 8 (11%) |
| History of tuberculosis | 19 (15%) | 17 (30%) | 2 (3%) |
| Takes cardiac medication | 82 (65%) | 25 (45%) | 57 (81%) |
| Nicotine smoking | 18 (14%) | 15 (27%) | 3 (4%) |
| Former mine worker | 29 (23%) | 28 (50%) | 1 (1%) |
| Symptoms and clinical examination | |||
| Oedema | 118 (94%) | 52 (93%) | 66 (94%) |
| Dyspnea | 115 (91%) | 53 (95%) | 62 (89%) |
| Chest pain | 27 (21%) | 9 (16%) | 18 (26%) |
| Irregular heart beat | 23 (18%) | 5 (9%) | 18 (26%) |
| Systolic blood pressure, mmHg, median (IQR) | 132 (113–149) | 126 (107–144) | 138 (118–151) |
| Diastolic blood pressure, mmHg, median (IQR) | 79 (68–92) | 78 (68–92) | 80 (70–96) |
| SpO2, %, median (IQR) | 91 (80–95) | 88 (76–92) | 93 (87–96) |
| Haemoglobin, g/dL, median (IQR) | 13 (11–15) | 14 (11–16) | 12 (11–14) |
Abbreviations: IQR (interquartile range), CM (cardiomyopathy), heart disease (heart disease), heart failure (heart failure)
The detailed echocardiographic data of the patients hospitalized due to heart failure are listed in S1 Table. Only 48% (60/126) had a normal sized LV. Left ventricular systolic function was preserved in 60% (75/126) of participants, but severely impaired in 22% (28/126). 29% (36/126) of patients had a ventricular hypertrophy and 24% (30/126) presented with left ventricular dilatation. Moderate to severe valve regurgitation of the aortic valve accounted for 5% (6/126) of patients and of the mitral valve for 13% (16/126) of patients. 2% (2/126) of patients had a moderate to severe aortic valve stenosis and 3% (4/126) of patients a moderate to severe mitral valve stenosis. Severe tricuspid insufficiency was noted in 15% (19/126) of patients. 31% (39/126) of patients had some pericardial effusion, but in only 5% (6/126) of patients this effusion was the cause of the heart failure (S1 Table).
The most frequent etiology for heart failures were chronic pulmonary heart disease (32/126, 25%), followed by dilated cardiomyopathy (21/126, 17%) and valvular heart disease (20/126, 16%) (Fig 2). Among the valvular heart diseases, most were rheumatic origin (Table 3). Coronary heart diseases accounted for 11% (14/126) and hypertensive heart diseases represented 9% (11/126) of all reasons for hospitalization due to heart failure (Fig 2 and Table 3). 4 patients died during the hospitalization: A 70 years old male with chronic pulmonary heart disease, a 18 years old male with a fulminant acute pulmonary heart disease, a 56 years old female with dilated cardiomyopathy and a 51 years old female with a valvular (rheumatic) heart disease.
Abbreviations: CM (cardiomyopathy), HD (heart disease), HF (heart failure).
Table 3
| Etiology | Total (N = 126) | Male (n = 56) | Female (n = 70) |
|---|---|---|---|
| Chronic pulmonary HD | 32 (25%) | 27 (48%) | 5 (7%) |
| Dilated CM | 21 (17%) | 5 (9%) | 16 (23%) |
| Post-partum CM | 3 (2%) | 0 (0%) | 3 (4%) |
| Valvular HD | 20 (16%) | 5 (9%) | 15 (21%) |
| Rheumatic HD | 12 (10%) | 4 (7%) | 8 (11%) |
| Coronary HD | 14 (11%) | 5 (9%) | 9 (13%) |
| Hypertensive HD | 11 (9%) | 5 (9%) | 6 (9%) |
| Functional HF | 8 (6%) | 4 (7%) | 4 (6%) |
| Acute pulmonary HD | 6 (5%) | 2 (4%) | 4 (6%) |
| Pericardial HD | 6 (5%) | 2 (4%) | 4 (6%) |
| Tuberculosis pericarditis | 4 (3%) | 2 (4%) | 2 (3%) |
| Non-tuberculosis pericarditis | 2 (2%) | 0 (0%) | 2 (3%) |
| Rhythmic HD | 5 (4%) | 1 (2%) | 4 (6%) |
| Hypertrophic CM | 2 (2%) | 0 (0%) | 2 (3%) |
| Unclassified CM | 1 (1%) | 0 (0%) | 1 (1%) |
Abbreviations: CM (cardiomyopathy), heart disease (heart disease), heart failure (heart failure)
Heart failure: Risk factors for the most common heart failure etiology
Chronic pulmonary heart disease was the most common etiology for heart failure among the hospitalized study population. Univariate logistic regression revealed that several patient characteristics were associated with chronic pulmonary heart disease with strongest associations for male, arterial hypertension, history of TB and former mine worker (S2 Table). When the multivariate logistic regression model was fitted with these variables, only a history of TB (adjusted odds ratio 6.25 [95% confidence interval 1.24–31.481]; p-value 0.026) and former mine worker (adjusted odds ratio 24.65 [95% confidence interval 5.06–120.101]; p-value <0.001) remained risk factors for chronic pulmonary heart disease.
Discussion
This retrospective cohort study included all echocardiograms (n = 352) performed during a 17-month period in 2020/21 at a rural hospital in Northern Lesotho. Among the 210 adult participants with a heart disease, hypertensive heart disease (30%), valvular heart disease (19%), chronic pulmonary heart disease (18%), dilated CM (12%) and coronary heart disease (8%) were the most common etiologies. Heart failure represented a substantial burden of hospitalizations with 11% of all hospitalized patients in the same period. Among the 126 hospitalized participants with heart failure, only 48% had a normal sized LV and only 60% had a preserved left ventricular systolic function. The most common etiologies were chronic pulmonary heart disease (25%), dilated CM (17%), valvular heart disease (16%, most rheumatic), coronary heart disease (11%) and hypertensive heart disease (9%). Former mine workers and people with a history of TB were more likely to have a chronic pulmonary heart disease.
In 2019, about 600’000 people in Africa died of heart failure due to a heart disease [2]. It is estimated that the burden of heart diseases will increase in the coming decade and that the under-diagnosis rate is high [3]. In order to tackle this health problem, it is of paramount importance to understand the etiologies and risk factors for heart diseases and heart failure in the region.
In line with a recent meta-analysis of 22 African studies, hypertensive heart disease is the most common heart disease [6]. Moreover, valvular (mostly due to rheumatic origin) and cardiomyopathies are common etiologies, whereas ischemic or coronary heart diseases are–different to the rest of the world–still rather an infrequent reason at 7% of all heart failure cases, similar to our findings [6]. What is striking in our study, is the high number of chronic pulmonary heart diseases: It was the third most frequent heart disease (18%) among all assessed patients (hospitalized and non-hospitalized) and the most frequent heart disease (25%) among hospitalized patients with heart failure.
A comparable prospective echocardiography cohort study conducted at a rural referral hospital in Tanzania concluded that hypertensive heart disease (41%), followed by valvular heart disease (18%), coronary heart diseases (18%) and cardiomyopathies (15%) were the most common heart diseases [16]. Similar to the meta-analysis, they observed only 5% of pulmonary heart diseases. In contrast, a recent South African study of 119 patients with heart failure documented 12% pulmonary heart diseases, indicating, that there might be a regional difference in etiologies [17]. Chronic pulmonary heart disease or cor pulmonale is a right heart failure caused by long-term high blood pressure in the lung arteries and right ventricle, whereas the left heart works normal [18]. Most commonly it results from chronic lung diseases such as chronic obstructive pulmonary disease (COPD) [18]. The mining sector in Lesotho and South Africa is one of the main industries for Basotho, especially the men. It is well documented that Basotho mine workers have a high risk of lung diseases such as TB, COPD and silicosis [19, 20]. While working conditions in the official mines have improved, illegal mining among Basotho has increased, as many South African mines have closed down or become less accessible for foreign workers [21]. Another reason for increased chronic lung diseases and thus resulting in pulmonary heart diseases, might be the exposure to indoor air pollution from biomass cooking fuels, a common practice in rural Lesotho. A meta-analysis concludes strong association of this cooking practice with COPD with highest risk in the African region [22]. HIV infection itself is a cause of pulmonary hypertension, was a risk factor in the univariate logistic regression analysis, is prevalent in the setting and thus, may have been contributing to the high proportion of this kind of heart disease [23].
Treatment options for patients with chronic pulmonary heart diseases are limited and unspecific: Improvement of the underlying cause (e.g. inhaled pulmonary vasodilator therapy and oxygen), relief of symptoms (e.g. diuretics), and prevention of complications (e.g. anticoagulation). While some of the study participants received diuretics, none were taking any medication to improve the lung function nor were anticoagulated. Awareness and knowledge about lung diseases and diagnostic equipment are scarce and anticoagulation is routinely not done due to expensive monitoring and medication.
Our study has several limitations. First, it is a retrospective cohort study based on available clinical data with the risk of sampling bias. That’s the reason why we have incomplete data for non-hospitalized patients and had to focus our risk factor analysis on hospitalized patients, i.e. with acute heart failure. Nevertheless, the echocardiographic diagnosis of the heart diseases was systematically available for all study patients. Moreover, the heart failure syndrome contributes most to the mortality of heart diseases, it is important to focus on this population, as done in similar studies [6]. Second, in our setting coronary angiography, myocardial scintigraphy, stress-echocardiography and myocardial biopsies are not available. Thus, the differentiation of cardiomyopathies was not possible, and diagnosis of coronary heart disease was based on medical history, clinical examination, electrocardiogram and echocardiogram only. Third, we had no data on lung function, indoor air pollution or other cardiovascular risk factors. More research is warranted in this area.
To our knowledge, this is the first echocardiographic study from Lesotho systematically assessing the etiology of heart diseases and one of few in southern Africa. Another strength is that the study was able to determine the burden of the heart failure syndrome at a typical referral hospital in the region and evaluate the most frequent causes and its risk factors. The findings offer important insights for the region.
In conclusion, this study established the causes of heart diseases and heart failure, which is important for prevention and subsequent clinical management. The leading cause of heart disease in this setting is hypertension and it is thus crucial to improve prevention, screening and treatment of hypertension. However, in contrast to (northern) African epidemiological studies, pulmonary heart disease is unexpectedly common. Former mine workers and people with a history of TB were more likely to have a chronic pulmonary heart disease. There is an urgent need to improve awareness and knowledge about lung diseases among the community as well as clinicians, make diagnostic and therapeutic options available and increase prevention measures to reduce TB and air pollution exposure in the mines and homes of people in southern Africa.
Supporting information
S1 Table
Echocardiography findings of patients hospitalized due to heart failure.(DOCX)
S2 Table
Association between characteristics and most common etiology for heart failure.(DOCX)
Acknowledgments
We would like to recognize the hard work of the staff at Seboche Mission Hospital and most importantly, we gratefully acknowledge the study participants.
Funding Statement
Alain Amstutz received his salary through a grant from the MD–PhD programme of the Swiss National Science Foundation (grant number 323530_177576). No further funding was involved. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Data Availability
The data relevant to this study are available from Zenodo at DOI: 10.5281/zenodo.7333586 (https://doi.org/10.5281/zenodo.7333586).
References
Decision Letter 0
12 Jul 2022
PONE-D-21-39404Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort studyPLOS ONE
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Reviewer #1: The authors conducted a retrospective cohort study for adult access to cardiology department in order to identify the leading cause of heart disease in this population
Interestingly, heart failure represented a substantial burden of hospitalizations and the most common etiologies were chronic pulmonary heart disease with former mine workers and people with a history of TB being more likely to have a chronic pulmonary heart disease
In order to tackle this health problem, the authors underline how it is paramount importance to understand the etiologies and risk factors for heart diseases and heart failure in the region.
Moreover, the high number of chronic pulmonary heart diseases is striking and it is relevant how more research is warranted in this area.
The definitions of hypertrophic cardiomyopathy and dilated cardiomiopathy aren’t correct.
A clinical diagnosis of HCM in adult patients can therefore be established by imaging with 2D echocardiography or cardiovascular magnetic resonance (CMR) showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle, in the absence of another cause of hypertrophy in adults (https://doi.org/10.1161/CIR.0000000000000937)
Dilated Cardiomyopathy is defined as presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment (J Am Soc Echocardiogr 2015;28:1-39)
Reviewer #2: I read with pleasure the manuscript “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, which aims to examine the occurrence, etiology and characteristics of heart diseases in Lesotho analyzing the echocardiographic data of a referral hospital.
The study is very interesting because currently in the literature there are no data on heart diseases in Lesotho and, taking into account that cardiovascular diseases are becoming a major cause of death in Sub-Saharan Africa, it is important that they are investigated.
However, I have to point out some issues that, in my opinion, need to be changed in order to accept and publish the scientific article:
- The study has a major limitation regarding the small number of patients. The data collected from January 2020 to May 2021 are not sufficient to describe the situation of heart diseases in an African State. Data collection should be extended retrospectively as much as possible or, if the echocardiographic laboratory was recently established, it could be useful to combine the data with those of another hospital in Lesotho.
- All the data collected with the echocardiogram were carefully described in the section “Echocardiography”, as well as the techniques used, but none of these data were reported in the manuscript. I don’t think it is necessary to describe these data so accurately for the purposes of the study that is being carried out and especially if they should not be included in the scientific article.
- In the section “Definitions”, it would be interesting to insert the guideline or bibliographic reference for each definition.
- In the table 1 there are incorrect numbers: the sum of females (n. 134) and males (n.84) with abnormal echocardiogram is 218 instead of 210, the sum of females (n. 87) and males (n. 30) with normal echocardiogram is 117 instead of 125.
- In addition, in the table 1 it is also necessary to specify the different type of congenital heart disease diagnoses in the children with an abnormal echocardiogram.
- In the section “Heart disease: Occurrence, characteristics and etiology”, is the sentence “of whom the majority (130/210; 64%) were female with a median age of 58 (interquartile range [IQR] 46-72) years old” correct? The data does not match with the data of table 1.
- In the section “Heart failure: Occurrence, characteristics and etiology”, is the sentence “the majority of patients hospitalized due to heart failure were female (56%; 70/126) and had a median age of 66 years old (IQR 54-76)” correct? The data does not match with the data of table 2.
- In the table 2 it would be better to divide the section of cardiovascular risk, the section of symptoms and the section of vital signs for greater clarity.
- In the supplement table 1, the sum of percentages in section LV size, LV systolic function, diastolic relaxation impairment of LV is 101% instead 100%.
- In addition, in the supplement table 1, regarding the LV systolic function and in particular the mild systolic heart failure, replace “LVEF 41-53%” with “LVEF 41-54%”.
- In the line 263 “table 3” should be changed with “supplement table 1”.
- During hospitalization for heart failure, which was the mean length of stay? Have there been any cardiovascular death and which were the causes? Could you add this additional data in the article?
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Reviewer #1: No
Reviewer #2: No
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Author response to Decision Letter 0
1 Aug 2022
Find the well-formatted response letter uploaded separately.
Response to Reviewers
Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study
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When submitting your revision, we need you to address these additional requirements.
1. Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming.
Response: We updated our manuscript to meet PLOS ONE’s style requirements
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Response: We updated our funding information and provided the grant number in the in all relevant sections
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Response: We are already preparing the anonymized dataset for upload onto Zenodo and will be ready with DOI in time.
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Response: We updated our manuscript to meet PLOS ONE’s style requirements
Reviewer #1:
1. The definitions of hypertrophic cardiomyopathy and dilated cardiomiopathy aren’t correct. A clinical diagnosis of HCM in adult patients can therefore be established by imaging with 2D echocardiography or cardiovascular magnetic resonance (CMR) showing a maximal end-diastolic wall thickness of ≥15 mm anywhere in the left ventricle, in the absence of another cause of hypertrophy in adults (https://doi.org/10.1161/CIR.0000000000000937). Dilated Cardiomyopathy is defined as presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension and valve disease) or coronary artery disease sufficient to cause global systolic impairment (J Am Soc Echocardiogr 2015;28:1-39)
Response: Thank you very much for spotting this important error from our side. We realized that there was a misunderstanding between the writing and the clinical team and the definitions for HCM and DCM were not correctly reflected. We adapted the definitions, added the corresponding guideline references and these were the definitions used by the clinical team during examination. We adapted accordingly in section “Definitions”:
Dilated cardiomyopathy. “LV or biventricular dilation and impaired contraction, not explained by abnormal loading conditions (e.g. hypertension and valvular heart disease) or coronary artery disease”
Hypertrophic cardiomyopathy. “A maximal end-diastolic wall thickness of ≥15 mm anywhere in the LV, in the absence of another cause of hypertrophy”
Reviewer #2:
1. I read with pleasure the manuscript “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, which aims to examine the occurrence, etiology and characteristics of heart diseases in Lesotho analyzing the echocardiographic data of a referral hospital. The study is very interesting because currently in the literature there are no data on heart diseases in Lesotho and, taking into account that cardiovascular diseases are becoming a major cause of death in Sub-Saharan Africa, it is important that they are investigated.
Response: Thank you very much for your positive feedback.
2. However, I have to point out some issues that, in my opinion, need to be changed in order to accept and publish the scientific article: The study has a major limitation regarding the small number of patients. The data collected from January 2020 to May 2021 are not sufficient to describe the situation of heart diseases in an African State. Data collection should be extended retrospectively as much as possible, or, if the echocardiographic laboratory was recently established, it could be useful to combine the data with those of another hospital in Lesotho.
Response: We agree with the reviewer that the data is limited. The echocardiography department was established in January 2020 (mentioned in the manuscript). The only other health facility in Lesotho that has an echocardiography department is in the capital, in Maseru. During the implementation of the echocardiography department, we were in contact with that hospital, however, they did not agree to share their data. We are planning to conduct an update of our data, but since there was a change of leadership in mid-2021 it became more difficult to collaborate. Despite these shortcomings, we believe that it is important to get this data out into the public – to at least have some initial data from Lesotho – and to stimulate more research about this topic in the country.
3. All the data collected with the echocardiogram were carefully described in the section “Echocardiography”, as well as the techniques used, but none of these data were reported in the manuscript. I don’t think it is necessary to describe these data so accurately for the purposes of the study that is being carried out and especially if they should not be included in the scientific article.
Response: We think that these details are important for two reasons. First, these details help to understand the echocardiography definitions we used and the results presented (Supporting Information S1 Table provides the details). Second, we think these details are crucial in case someone wants to reproduce our study findings. However, we understand the reviewers concern and think this paragraph is too prominent in the main manuscript. Thus, we moved this entire paragraph into the Supporting Information (S1 Text) and added a sentence in section “Definitions”:
“We provide detailed information about the echocardiography machine, techniques and measurements used in S1 Text.”
4. In the section “Definitions”, it would be interesting to insert the guideline or bibliographic reference for each definition.
Response: We added the respective guideline/reference for each definition.
5. In the table 1 there are incorrect numbers: the sum of females (n. 134) and males (n.84) with abnormal echocardiogram is 218 instead of 210, the sum of females (n. 87) and males (n. 30) with normal echocardiogram is 117 instead of 125.
Response: Thank you for pointing out this important typo. We corrected the numbers.
6. In addition, in the table 1 it is also necessary to specify the different type of congenital heart disease diagnoses in the children with an abnormal echocardiogram.
Response: We added the details of these 3 congenital heart diseases in the footnote of Table 1:
“[1] Congenital heart diseases: 1 girl with an aortic stenosis (bicuspid aortic valve) and 1 girl and 1 boy with a patent ductus arteriosus”
7. In the section “Heart disease: Occurrence, characteristics and etiology”, is the sentence “of whom the majority (130/210; 64%) were female with a median age of 58 (interquartile range [IQR] 46-72) years old” correct? The data does not match with the data of table 1.
Response: Thank you for spotting this typo. It was related to the above typo and the median age was wrongly taken from the overall population instead of only the population with abnormal echocardiogram. We corrected the numbers.
8. In the section “Heart failure: Occurrence, characteristics and etiology”, is the sentence “the majority of patients hospitalized due to heart failure were female (56%; 70/126) and had a median age of 66 years old (IQR 54-76)” correct? The data does not match with the data of table 2.
Response: This is correct and matches the data of table 2. There were a total of 126 hospitalized patients due to heart failure (Total in first column), they had a median age of 66 years with an IQR 54-76 (median age in first column) and 56% were female (n=70/126, third column).
9. In the table 2 it would be better to divide the section of cardiovascular risk, the section of symptoms and the section of vital signs for greater clarity.
Response: We thank the reviewer for this great suggestion and adapted accordingly.
10. In the supplement table 1, the sum of percentages in section LV size, LV systolic function, diastolic relaxation impairment of LV is 101% instead 100%.
Response: This was due to rounding. We added one decimal digit everywhere to avoid misleading sums due to rounding.
11. In addition, in the supplement table 1, regarding the LV systolic function and in particular the mild systolic heart failure, replace “LVEF 41-53%” with “LVEF 41-54%”.
Response: Thank you for spotting this. The mistake was not adding a ‘greater than or equal sign’ in front of LVEF 54%. We corrected accordingly to “LVEF ≥ 54%”.
12. In the line 263 “table 3” should be changed with “supplement table 1”.
Response: We adapted accordingly.
13. During hospitalization for heart failure, which was the mean length of stay? Have there been any cardiovascular death and which were the causes? Could you add this additional data in the article?
Response: Unfortunately, our retrospective data collection tool did not include length of hospitalization. However, we do have the mortality data. We added a short paragraph just before section “Heart failure: risk factors for the most common heart failure etiology” to summarize this data:
“4 patients died during the hospitalization: A 70 years old male with chronic pulmonary heart disease, a 18 years old male with a fulminant acute pulmonary heart disease, a 56 years old female with dilated cardiomyopathy and a 51 years old female with a valvular (rheumatic) heart disease.”
Attachment
Submitted filename: ECHO_response_to_reviewers.docx
Decision Letter 1
16 Nov 2022
Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study
PONE-D-21-39404R1
Dear Dr. Amstutz,
We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.
Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.
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Roberto Magalhães Saraiva, MD, PhD
Academic Editor
PLOS ONE
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Reviewer #2: All comments have been addressed
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2. Is the manuscript technically sound, and do the data support the conclusions?
The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.
Reviewer #2: Yes
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3. Has the statistical analysis been performed appropriately and rigorously?
Reviewer #2: Yes
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Reviewer #2: Yes
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Reviewer #2: Yes
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6. Review Comments to the Author
Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)
Reviewer #2: I read the reviewed version of the article “Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): a retrospective echocardiography cohort study”, a retrospective cohort study which treats etiology, characteristics and occurrence of heart disease in Lesotho analyzing data from an echocardiography department. The comments raised in the previous review have been addressed as far as possible and, in my opinion, now this manuscript is acceptable for publication, aware of the fact that the small number of patients cannot fully represent the situation of heart disease in an African State. Maybe the article title should be changed to “a preview of a retrospective echocardiography cohort study” hinting at the intention to continue the study increasing the number of patients.
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7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files.
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Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy.
Reviewer #2: No
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Acceptance letter
7 Dec 2022
PONE-D-21-39404R1
Etiology, characteristics and occurrence of heart diseases in rural Lesotho (ECHO-Lesotho): A retrospective echocardiography cohort study
Dear Dr. Amstutz:
I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department.
If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact gro.solp@sserpeno.
If we can help with anything else, please email us at gro.solp@enosolp.
Thank you for submitting your work to PLOS ONE and supporting open access.
Kind regards,
PLOS ONE Editorial Office Staff
on behalf of
Dr. Roberto Magalhães Saraiva
Academic Editor
PLOS ONE