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CFTR is expressed in cardiac myocytes. In mice, lack of CFTR alters cardiomyocyte contraction and Ca2+ signaling, and decreases cardiac reserve. We undertook a pilot study evaluating left ventricular (LV) function in CF patients using strain and strain rate echocardiography.
Methods
Echocardiography with tissue Doppler and strain and strain rate imaging were performed in 8 CF adults following pulmonary function tests. Results were compared to literature values obtained in healthy subjects.
Results
All CF individuals had normal LV ejection fractions. In contrast, 50% of men and 100% of women with CF had decreased LV systolic strain. Strain rates were significantly decreased in 100% of CF individuals. RV function was normal and LV function did not correlate with lung function.
Conclusions
Strain and strain rate echocardiography identified LV systolic abnormalities in CF individuals not detected by conventional echocardiography. We propose that this echocardiography modality may identify subclinical cardiac dysfunction in CF.
Cystic fibrosis (CF), the most common autosomal recessive lethal disease in Caucasians, causes obstructive lung disease and can lead to cor pulmonale with right ventricular (RV) dysfunction. Presence of the cystic fibrosis transmembrane conductance regulator (CFTR) in cardiac myocardium [
] has prompted debate regarding possible defective ion channel induced cardiomyopathy. Clinical heart disease in CF is rare, restricted to case reports and post-mortem findings [
]. It has been unclear if this is due to lack of physiological importance of CFTR in the heart, relatively short lifespan of those with CF, or a technical inability to detect subclinical disease. Clinical investigations into the cardiac health of individuals with CF have been complicated by significant lung disease and its resultant secondary effects on heart function. However, with increased survival of individuals with CF and the development of technology to detect subclinical cardiac dysfunction, evaluating adult CF patients for possible CF-induced cardiomyopathy has become feasible.
Transthoracic echocardiography is the routine clinical method for evaluation of heart function. Standard echocardiography uses motion parameters, displacement and velocity, to assess global function, however it has significant pitfalls. Lack of movement in a discrete area may be missed as translational movement of neighboring myocardial segments may give the false impression of normal myocardial contractility. Echocardiography using strain and strain rate techniques has been developed to complement and enhance conventional echocardiography's ability to detect impaired heart function. Strain imaging measures regional deformation of the myocardium and strain rate is the velocity of deformation. In contrast to displacement, measurements of deformation are less affected by translational movements. An additional advantage of strain imaging is that it is less dependent on loading conditions than other standard measurements of systolic function, such as left ventricular ejection fraction [
We undertook a pilot study to determine if strain rate echocardiography can be used to identify subclinical cardiac disturbances in individuals with CF. We focused our study on LV function in order to better understand the cardiac function in CF, independent of lung function.
2. Methods
2.1 Human subjects
The institutional review boards of the University of Illinois, Urbana-Champaign and Carle Foundation Hospital approved the following prospective cohort study. Potential subjects were recruited from the CF Clinic at Carle Hospital, a combined pediatric and adult CF Foundation accredited center. All subjects signed IRB approved consents to participate in the study, which was independent of the care they received through the CF Clinic. Inclusion criteria included: age ≥ 18 years of age and confirmed diagnosis of CF by positive sweat test and/or homozygous for disease causing CFTR mutation. Exclusion criteria included: sudden change in pulmonary function as defined by a ≥10% decline in FEV1 or a suspected acute infection. Supplementary Fig. 1 describes subject recruitment and study design. Subjects were asked to undergo a venous blood draw by phlebotomists at the Carle Clinical Laboratory and an echocardiogram was performed at the Carle Heart Center. Nine subjects signed consents with one subject being lost to follow-up contact, resulting in eight subjects completing all parts of the study. Echocardiograms and venous blood draws were scheduled within 1 week of CF Clinic appointments (7/8 within 24 h), where pulmonary function tests were performed. Characteristics of individuals who participated in the study are included in Table 1. Data were obtained from their recent CF Clinic visit prior to echocardiogram.
Table 1Cohort characteristics.
Characteristics
CF Cohort (n = 8)
Age (years)
35 ± 13 (35)
Gender (M:F)
6:2
BMI (kg/m2)
26.6 ± 10.2 (24)
CF genotypes
ΔF508/ΔF508
5
ΔF508/R117H
1
ΔF508/D1152H
1
ΔF508/1898 + 1G- > A
1
FEV1 (%)
68 ± 27 (61)
Last CF exacerbation requiring hospitalization/ER visit (years)
6.2 ± 5.1 (5.8)
Subjects with CF-related diabetes
1
HR (beats/min)
75 ± 17 (76)
Systolic BP (mm Hg)
129 ± 11 (128)
Diastolic BP (mm Hg)
76 ± 9 (74)
BNP (pg/mL)
20 ± 11 (20)
Data are presented as means ± SD. Median values are in parenthesis.
Transthoracic echocardiography with tissue Doppler was performed by a single registered diagnostic cardiac sonographer (L.M.) and read by a single board-certified cardiologist (A.B.), both of which were blinded to the clinical characteristics of each subject. Images were obtained using a Philips iE33 xMATRIX echocardiography machine with an s5-1 transducer (Andover, MA). Two-dimensional echocardiographic images were obtained in standard parasternal, apical and subcostal views. At end-diastole, left ventricular end diastolic dimension (LVED), interventricular septal thickness (IVS), and posterior wall thickness (LVPW) were measured at the level of left ventricular minor dimension. At end-systole, left ventricular end systolic dimension (LVESD) and left atrial (LA) dimensions were obtained. Left ventricular systolic function was determined by calculating left ventricular ejection fraction (LVEF) by Simpson's formula in the apical 2 and 4-chamber views. LVEF was also visually estimated by reviewing segmental wall motion in all images. Aortic root size was measured in diastole at maximal dimension at the level of the Sinus of Valsalva. Right ventricular size was measured at the basal and mid-cavity levels at end-diastole in the apical 4-chamber view. All subject data were within normal limits and RV base diameter is presented herein. Right ventricular systolic function was assessed by tricuspid annular plane systolic excursion using M-mode echocardiography and determined to be qualitatively “normal” or “abnormal.” Measurement of left atrial volume was performed in the apical 2 and 4-chamber views at ventricular end-systole. Cardiac valves were visualized by 2D echocardiography and flow patterns were assessed by color, continuous, and pulsed wave Doppler. Medial and lateral isovolumetric relaxation times (IVRT) were measured by continuous wave Doppler, with each site representing the average of 3 consecutive cardiac cycles. The reported IVRT represents the average of both sites. Mitral inflow was interrogated by continuous and pulse wave Doppler measuring E and A velocities and deceleration time (DT). We measured myocardial E′ and A′ velocities at medial and lateral aspect of the mitral annulus by tissue Doppler in the apical 4-chamber view. Color tissue Doppler imaging (TDI) of the left and right ventricle were acquired in apical 2 and 4-chamber views at high frame rate (minimum 90 Hz) by reducing depth and sector width. Care was taken to avoid reverberation artifacts. At least 3 consecutive cycles were recorded.
2.3 Strain and strain rate
Data was analyzed off-line by QLAB software (Phillips Medical System) to obtain myocardial strain and strain rate data. Tissue Doppler recordings with the best image quality were chosen for further analysis. All images were of diagnostic quality. Curved M-mode lines of the ventricles were drawn from basal septum to basal lateral segment in the apical 4-chamber view, from basal inferior to basal anterior segment in the 2-chamber view, and from the lateral to medial side of the tricuspid annulus in the 4-chamber view. Global peak systolic strain and strain rate, early and late diastolic strain rate values of the left and right ventricles were identified as the nadir of these curves. Time to peak systolic strain and strain rate were measured from R-wave on the electrocardiogram to the nadir of curves. Strain is defined, as the deformation of an object, relative to its original length, and is expressed in percent. Positive strain represents lengthening or stretching, and negative strain is shortening or compression, in relation to the original length. Similarly, strain rate is negative during shortening and positive during elongation, and expressed as s−1. Test re-test reliability using measurements from four individuals yielded intraclass coefficients of 0.84 for strain and 0.85 for strain rate. Intraclass coefficient >0.80 is considered excellent reliability between repeated measures.
2.4 Statistics
Data obtained from CF subjects was compared to reference values obtained from normal values established in the published literature. Conventional echocardiographic normal values and definitions of dysfunction were obtained from international guidelines set forth by the American Society of Echocardiography and the European Association of Echocardiography [
]. Systolic strain and strain rates for healthy controls were obtained from the HUNT study, which consisted of 1266 Norwegian men and women without cardiovascular disease [
]. When appropriate, normal values for age and/or gender were utilized. To determine significance at P < 0.05, CF subject values were required to be outside of 95% confidence intervals, thus being at least 2 standard deviations beyond mean values. We performed additional analyses to compare our results to the control groups in studies by Stoylen et al. (diastolic strain rate) [
Left and right ventricular strain and strain rate measurement in normal adults using velocity vector imaging: an assessment of reference values and intersystem agreement.
All interested CF adults seen at the Carle CF Clinic that met study criteria were enrolled into our study over a 1-year timespan. Out of a total of 24 adult potential subjects, 12 were interested in participating, with 10 meeting study criteria. Ultimately, 9 individuals signed consents, with 8 completing the study (Supplementary Fig. 1). Characteristics of the 8 subjects who participated in the study are presented in Table 1. All subjects had at least one copy of ΔF508, with 5/8 subjects being homozygous for this mutation. None of our subjects had an acute visit to the hospital (ED or inpatient admission) for acute respiratory distress for at least 3 months. The majority of our subjects (6/8) had not required a hospital admission for a CF pulmonary exacerbation for 3–12 years, with a mean of 6.2 years. There was a wide range of pulmonary function (39–106%), 3 with normal or mild, 2 with moderate, and 3 with severe obstructive lung disease according to GOLD criteria. The majority of our subjects had BMIs between 18 and 25 kg/m2, however, we did have 3 individuals with BMIs >25 (26.5, 29.7, and 50.1). Only one individual had been diagnosed with CF-related diabetes due to an abnormal oral glucose tolerance test. From a cardiovascular perspective, subjects were generally healthy with no tachycardia, 75% of individuals with SBP < 140 (2 subject with SBPs of 142, 143) and all but one with DBP < 90 (91), and 100% with normal BNP (<100 pg/mL). None of our subjects had previously seen a cardiologist, taken cardiovascular modifying medications, or received a work-up for possible cardiovascular disease. There was no difference in age, BMI, FEV1, time since exacerbation, HR, DBP, or BNP between men and women. The female cohort did have a significantly lower SBP than male counterparts (116 ± 8 vs. 133 ± 9, P = 0.04). There was no significant difference in any of the cohort characteristics between those ≤40 years old and those >40 years old, except for age (27 ± 7 vs. 49 ± 6, P = 0.004).
3.2 Conventional 2D echocardiography
We first measured cardiac structure and function via conventional 2D echocardiography (Table 2). No individuals showed RV hypertrophy, however, 50% of individuals had upper limit of normal or mildly abnormal LVPW and/or IVS measurements. Examination of global ventricular systolic function by conventional echocardiography revealed qualitatively normal RV function in all 8 subjects. LV systolic function was also normal in all subjects, with a mean LV ejection fraction of 61 ± 4% (Reference: ≥55%) (Supplementary Fig. 2). One subject had mild mitral regurgitation, otherwise there were no valvular abnormalities.
Table 2Structural measurements using conventional echocardiography.
Measurements
CF men (n = 6)
Reference men
CF women (n = 2)
Reference women
IVS (cm)
1.0 ± 0.1
≤1.0
1.0 ± 0.1
≤0.9
LVPW (cm)
1.0 ± 0.1
≤1.0
1.0 ± 0*
≤0.9
LA diameter (cm)
3.1 ± 0.2
≤4.0
3.3 ± 0.0
≤4.0
Aorta (cm)
2.7 ± 0.2
≤4.5
2.8 ± 0.2
≤4.5
RV base (cm)
3.3 ± 0.3
<4.2
3.1 ± 0.2
<4.2
Normal reference values for LV dimensions (IVS: interventricular septum, LVPW: LV posterior wall, LA: left atrium) are presented by gender, whereas those for RV are combined. Data expressed as means ± SD. Asterisk denotes mean values outside of reference range.
Subsequently, we examined LV diastolic dysfunction with measurements presented in Table 3. All subjects had a prolonged deceleration time (DT) with the overall mean being 265 ± 42 ms. While most individuals had 1–2 abnormal parameters, 3/8 subjects had at least two abnormal diastolic measurements that were consistent with LV diastolic dysfunction. These individuals showed some degree of diastolic dysfunction, with an E/A approaching or greater than 2, IVRT < 60 ms, lateral e′ < 8.5 cm/s and lateral E/e′ > 12.
Table 3Diastolic measurements using conventional echocardiography.
Measurements
CF ≤ 40 (n = 5)
Reference ≤40
CF > 40 (n = 3)
Reference >40
E/A
1.93 ± 0.72
1.53 ± 0.40 (0.73–2.33)
1.08 ± 0.22
1.28 ± 0.25 (0.78–1.78)
DT (ms)
251 ± 20*
166 ± 14 (138–194)
288 ± 64*
181 ± 0.19 (143–219)
IVRT (ms)
51 ± 7
67 ± 8 (51–83)
65 ± 13
74 ± 7 (60–88)
Septal e′ (cm/s)
9.9 ± 4.0*
15.5 ± 2.7 (10.1–20.9)
10.4 ± 2.0
12.2 ± 2.3 (7.6–16.8)
Lateral e′ (cm/s)
8.2 ± 3.9*
19.8 ± 2.9 (14.0–25.6)
10.7 ± 1.1*
16.1 ± 2.3 (11.5–20.7)
Septal E/e′
10.8 ± 4.2
<8–15
7.5 ± 1.4
<8–15
Lateral E/e′
13.6 ± 5.8*
<8–12
7.3 ± 1.8
<8–12
Reference values are by age. Values are presented as means ± SD with values in parenthesis representing 95% confidence intervals. Asterisk denotes mean values outside of reference range.
To determine if subclinical LV dysfunction exists in CF adults, we measured LV strain and strain rate through post-acquisition analysis of TDI. Representative images are seen in Supplementary Fig. 3. We found that 50% of men and 100% of women with CF had LV systolic shortening that was less than the 95% confidence interval ranges for healthy individuals, as evidenced by decreased negative values (Fig. 1A ). Mean and standard deviation LV strain for men with CF was −11.7% ± 3.2% vs. −15.9% ± 2.3% for healthy controls. For women with CF, LV strain was −11.7% ± 1.6% vs. −17.4% ± 2.3% for control subjects. Time to peak strain was 373 ± 26 ms (mean ± SD). LV deformation via strain rate imaging found that 100% of CF individuals had significantly decreased shortening velocity (Fig. 1B). Mean peak systolic strain rate and SD for men and women with CF was −0.56 ± 0.10 and −0.49 ± 0 s−1vs. −1.01 ± 0.13 and −1.05 ± 0.13 s−1, respectively, for controls. Time to peak strain rate was 124 ± 31 ms (mean ± SD).
Fig. 1LV strain (A) and strain rates (B) of CF subjects according to gender and age. Individual symbols represent values from individual CF subjects. Symbols with error bars represent values from reference healthy controls, with the symbol representing the mean value and error bars representing 95% confidence intervals. For reference values, males < 40, n = 126; females < 40, n = 208; males > 40, n = 327; females > 40, n = 336.
To account for any variation in the method and/or vendor used in our study and that of the HUNT study, we also compared our data to that of Labombarda et al., who used the exact same method and software system as we did. Systolic strain (−11.7% ± 2.7% vs. −18.8% ± 3.7%, P < 0.001) and strain rates (−0.50 ± 0.09 vs. −0.90 ± 0.50 s−1, P < 0.01) were significantly less in our CF cohort than that in the control group from Labombarda et al. [
Although less studied than systolic strain rate, diastolic strain rate can also be measured from TDI. We examined LV diastolic strain rate during early LV filling (Peak E) and atrial systole (Peak A). We found that mean peak E with SD for CF subjects were 0.93 ± 0.15 s−1, while peak A was 0.59 ± 0.20 s−1 (n = 7). Compared to control subjects in the study by Stoylen et al. [
], 57% of our CF subjects had decreased strain rate during early filling (2.22 ± 0.49, n = 28) and atrial systole (1.49 ± 0.48, n = 28).
3.4 RV strain and strain rate
While not the focus of this study, we also acquired RV strain and strain rate measurements. For our CF subjects RV strain (mean ± SD) was −13.9% ± 4.6%, with a time to peak of 340 ± 0.04 ms. RV strain rate was −0.56 ± 0.16 s−1, with time to peak being 121 ± 23 ms. A prior study of healthy volunteers by Fine et al. found a RV strain of −20.4% ± 3.2% and strain rate of −1.2 ± 0.2 s−1 (mean ± SE, n = 128) [
Left and right ventricular strain and strain rate measurement in normal adults using velocity vector imaging: an assessment of reference values and intersystem agreement.
To determine if any of our findings with LV or RV strain and strain rates correlated with FEV1, we undertook correlation analysis, calculating Pearson correlation coefficients (r value). We found that there were no significant (P > 0.05) correlations between low FEV1 and decreased LV or RV strain (rate) (Fig. 2).
Fig. 2Correlation analysis between LV and RV strain and strain rates and FEV1. Symbols represent values from individual CF subjects. Line represents that from regression analysis. Pearson correlation (r value) and P values are indicated for each analysis. A and B represent LV systolic strain and strain rate, respectively. C and D represent RV systolic strain and strain rate, respectively.
The current study contributes to the advancement of our knowledge regarding the heart function of individuals with CF. While there have recently been two studies using strain imaging echocardiography to examine RV or LV function [
], each study only focused on a subset of echocardiographic measurements. Here, for the first time, we have provided a comprehensive examination of heart function, providing measurements of RV, LV, diastolic, and systolic function, with a comparison between tissue Doppler, strain, and strain rate echocardiography. From these measurements we have shown that despite normal indices of systolic function by conventional echocardiography, strain and strain rate echocardiography have identified LV systolic dysfunction in adults with CF. We have also shown that these abnormalities occur independent of lung function, which supports the idea of a primary cardiomyopathy.
Observations of cardiac pathologies in CF were first reported in 1946 with that of RV hypertrophy secondary to pulmonary disease [
]. Since then there has been a consensus regarding the potential for RV structural and functional abnormalities to occur in CF due to progressive chronic obstructive disease and increased pulmonary pressures. However, there has been a lack of understanding regarding potential LV abnormalities in CF. This knowledge gap has not been due to a lack of study. Reports of ventricular arrhythmias, cardiomyopathy, sudden cardiogenic death, and LV myocardial fibrosis and necrosis [
Conventional echocardiography, as the primary modality for studying cardiac function, has several shortcomings, as described previously. In contrast, strain and strain rate echocardiography have emerged as tools to assess function through measuring regional deformation. With conventional echocardiography we found that CF subjects had normal ejection fractions. With this information alone, one might come to the conclusion that no cardiac abnormalities exist. However, strain and strain rate were significantly decreased in CF subjects, indicating abnormal systolic function. Labombarda et al. also found decreased LV strain and strain rate in CF subjects with normal ejection fractions [
]; results similar to what we found in our current study. In addition to systolic function, LV diastolic function in CF has been studied with conventional Doppler echocardiography, with mixed results [
]. In our study, we found that 38% of our subjects had LV diastolic dysfunction by conventional echocardiography, whereas 57% had abnormal diastolic strain rate. While Labombarda et al. found no diastolic dysfunction with Doppler echocardiography, diastolic strain rate showed significant diastolic dysfunction in CF subjects compared to controls [
]. These discrepancies are likely due to increased sensitivity of strain and strain measurements to detect early cardiac disease. For this reason, it has been proposed that strain and strain rate measurements be used as screening tools for detection of subclinical cardiomyopathy, such as in amyloidosis [
Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis.
]. For amyloidosis, Koyama et al. have shown that strain imaging detects cardiac dysfunction in individuals that will develop heart failure prior to conventional tissue Doppler, where abnormalities do not become apparent until heart failure has developed. As a result of this, they have shown that strain imaging is a better predictor of clinical outcome and mortality than conventional tissue Doppler [
Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis.
]. Similar longitudinal studies in CF are necessary to determine the prognostic value of strain rate imaging to detect clinically relevant heart disease.
In contrast to Labombarda et al., we found no correlation between LV strain (rate) measurements and FEV1. Labombarda et al. observed significant correlation between low FEV1 and decreased septal wall strain and strain rates [
]. It is possible that the differences in our findings are related to the small number of subjects in our study. However, it is also possible that their findings are reflective of worse RV function in their CF subjects, since their CF subjects had significantly increased RV wall thickness, whereas the subjects in our study had normal RV measurements. This is supported by the observation that their septal strain rate correlation with FEV1 was highly significant (r = −0.68, P < 0.001), whereas lateral strain rate correlated less and was not significant (r = − 0.41, P < 0.062). Furthermore, in Ozcelik et al.'s examination of RV function, their CF subjects had normal RV structure and there was no correlation between strain (rate) measurements and FEV1 [
]. Since hypoxemia and poor RV function from pulmonary disease can affect LV function, understanding the potential correlation between FEV1 and strain (rate) measurements is important to study further in order for it to be used as a modality for those with CF.
Our study, together with prior human and mouse studies, suggests that there is an inherent defect in CF cardiac muscle that causes ventricular dysfunction. The presence of CFTR in cardiac myocytes has been known for over 20 years [
]. Disruption of CFTR function in murine cardiomyocytes causes increased intracellular Ca2+ and enhanced reliance on CAMKII and Ca2+-activated Cl− channels to compensate for loss of CFTR ion transport [
The cardiac-specific nuclear delta(B) isoform of Ca2+/calmodulin-dependent protein kinase II induces hypertrophy and dilated cardiomyopathy associated with increased protein phosphatase 2A activity.
]. Doppler echocardiography and catheterization of murine ΔF508 CFTR left ventricles showed LV hypertrophy, hyperdynamic hearts, and decreased cardiac reserve upon dobutamine stimulation [
]. While more work is necessary to fully understand the cellular and molecular changes that occur in CF myocardium and the physiologic implications, these studies give insight into potential mechanisms of cardiac dysfunction in CF.
Our study has several limitations. First, we examined a small cohort of individuals. Due to the small population of CF patients seen within the regional center used in this study, patient recruitment was limited. While small in number, our selection criteria were formed in order to exclude patients with acute pulmonary exacerbations, which could confound our results. Second, our study did not include internal controls, like that of prior studies [
]. Instead we used data from the HUNT study, which consisted of 1266 Norwegian men and women without cardiovascular disease. This is the largest study to date to examine heart function with strain imaging in a healthy population. The fact that it is a cohort of predominantly Caucasians supports its use in our cohort of subjects. We do not have any information about the presence of individuals with CF in the HUNT study, however, given that the incidence of CF in Norway is ~1:4000, we consider the HUNT cohort essentially a “non-CF” cohort. Third, we used a single modality of strain (rate) imaging. There are several different modalities of strain (rate) imaging, including tissue Doppler and speckle tracking, each allowing the designation of different regions of interest (ROI). The primary cohort in the HUNT study used a combination of TDI and speckle tracking, while we used TDI with tracked ROI. Within the HUNT study they also compared TDI plus speckle tracking to TDI with tracked ROI with a smaller cohort. They found no difference in strain measurements, but TDI with tracked ROI strain rates were significantly more negative than TDI plus speckle tracking [
] (Supplemental Table 1). Since these values were more negative than the ones we used, using them does not affect our analysis and interpretation. However, using this smaller cohort would preclude us from analyzing data by gender and age, both of which can affect strain and strain rate [
]. Finally, it is important to note that there may be variation in the determination of strain and strain rate values by different software manufacturers. The HUNT study utilized a system by General Electronics, whereas ours used one from Philips. However, in comparing our data with that from Labombarda et al., who used the same Philips system as we did, we continued to see significant differences in strain and strain rate between CF and control cohorts (Supplemental Table 1), thereby supporting our original conclusions that strain and strain rate is abnormal in CF adults.
Our study also has several strengths. First, it independently validates the previous findings by Labombarda et al., thereby providing further evidence for heart dysfunction in CF. Second, it addresses a shortcoming of the Labombarda study, the healthiness of their CF cohort. Our cohort had less incidence of diabetes (1 vs. 7 patients), no evidence of RV hypertrophy, and no subjects on supplemental oxygen. In contrast, Labombarda's CF cohort had significantly increased RV wall thickness, with 10% of their subjects on supplemental oxygen. This is important because of the long-standing question as to whether there is a primary component of cardiac dysfunction in CF or it is purely secondary to non-cardiac phenomenon. Thus, our study for the first time provides a “healthy” cohort of CF subjects, which continue to show cardiac dysfunction.
Historically, individuals with CF did not have significant risk factors for cardiovascular disease. However, other than the likelihood of CF-induced cardiomyopathy, due to prolonged survival, CF individuals now may also have several other risk factors for cardiovascular disease: age, diabetes, increasing rates of obesity [
]. Thus, it is now more important than ever that attention be given to the cardiac health of individuals with CF. Our study, coupled with that of others [
], provides support for the use of strain and strain rate echocardiography to detect subclinical cardiac dysfunction in CF patients. Its increased sensitivity, decreased load-dependency, and ability to examine regional function independent of translational motion make this modality better suited than traditional echocardiographic measurements in detecting cardiac pathology in CF. Similar to other disease processes recently recognized in CF adults (e.g. colon cancer and osteoporosis), as we learn more about heart disease in CF, many new questions emerge. Does heart disease occur early in CF adults and/or present different than adults without CF? Is screening necessary, and if so, what modality is best and at what age? Do certain mutations lead to worse heart function and are individuals who are heterozygous for CFTR mutations at increased risk for heart disease than those without CFTR mutations? Regardless of the answers, research into questions like these will help advance our understanding of heart function in CF and lead to improvements in clinical care, helping to continue to increase the quality and longevity of life for those with CF.
Acknowledgments
We would like to thank the staff of the Cystic Fibrosis Clinic at Carle Foundation Hospital for their assistance in patient recruitment. This study was funded by a Carle Foundation Hospital Research Seed Grant to Z.M.S. and A.B.
Left and right ventricular strain and strain rate measurement in normal adults using velocity vector imaging: an assessment of reference values and intersystem agreement.
Longitudinal myocardial function assessed by tissue velocity, strain, and strain rate tissue Doppler echocardiography in patients with AL (primary) cardiac amyloidosis.
The cardiac-specific nuclear delta(B) isoform of Ca2+/calmodulin-dependent protein kinase II induces hypertrophy and dilated cardiomyopathy associated with increased protein phosphatase 2A activity.
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