Novel advanced cardiovascular magnetic resonance imaging study in women with gestational diabetes mellitus and preeclampsia

Pregnant women represent an under-investigated population in clinical research and the mechanisms of long-term cardiovascular complications in women with obstetric complications remain to be elucidated. This is the basis which stemmed our interest in conducting our research in pregnant women with gestational diabetes mellitus (GDM) and preeclampsia(pE). A third of parous women experience adverse pregnancy outcomes; an increased risk of heart failure, stroke and ischemic heart disease. GDM and pE are the leading obstetric complications of pregnancy. Both are associated with a substantial increase in the risk of long-term cardiovascular disease. The aims of my longitudinal cohort study were to assess maternal cardiac alterations during the third trimester of pregnancy and their recovery twelve-months post-partum in women with GDM (n=30) or pE (n=22) compared to women with healthy pregnancies (HP)(n=38). Phosphorus-magnetic resonance spectroscopy (31 P-MRS) and cardiovascular magnetic resonance imaging (CMR) were used to define myocardial phosphocreatine to ATP ratio (PCr/ATP), tissue characteristics, left ventricular (LV) volumes, mass, ejection fraction (EF), global longitudinal shortening (GLS), and diastolic function (mitral in-flow E/A ratio). Participants were monitored to birth, baby birth weights were recorded, placental tissue histology was assessed. Investigations were repeated 12-months postpartum to monitor cardiac changes. With obesity as a major and common risk factor for both GDM and pE, ten overweight and ten normal-weight nulliparous women were recruited as non-pregnant control groups. These studies have demonstrated that despite distinct etiologies, women with GDM and pE exhibit a similar myocardial phenotype during and after pregnancy with persistent subtle abnormalities in myocardial PCr/ATP ratio, LV mass and GLS compared to women with HP during pregnancy and twelve months’ postpartum assessments. Women with GDM and pE show similar myocardial alterations to nulliparous women with obesity, suggesting that the maternal myocardial changes are predominantly driven by obesity-associated metabolic dysfunction. In summary, the work in this thesis demonstrates the role of CMR and MRS in elucidating the cardiac structural, functional and energetic abnormalities in pregnancies complicated with gestational diabetes and preeclampsia. Most importantly, this work highlights that the persistent myocardial changes seen in women with GDM and pE at 12 months are mainly driven by obesity-associated metabolic dysfunction. With obesity becoming a huge worldwide health burden, it is very crucial to create societal awareness to support patients for a healthier lifestyle. This can be implemented through evidence based medicine and population based policies. Further research can be conducted to identify patients at risk and implement lifestyle interventions early to avoid long term complications to both the mother and fetus

Association between type 2 diabetes and changes in myocardial structure, contractile function, energetics, and blood flow before and after aortic valve replacement in patients with severe aortic stenosis

BACKGROUND: Type 2 diabetes (T2D) is associated with an increased risk of left ventricular dysfunction after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). Persistent impairments in myocardial energetics and myocardial blood flow (MBF) may underpin this observation. Using phosphorus magnetic resonance spectroscopy and cardiovascular magnetic resonance, this study tested the hypothesis that patients with severe AS and T2D (AS-T2D) would have impaired myocardial energetics as reflected by the phosphocreatine to ATP ratio (PCr/ATP) and vasodilator stress MBF compared with patients with AS without T2D (AS-noT2D), and that these differences would persist after AVR. METHODS: Ninety-five patients with severe AS without coronary artery disease awaiting AVR (30 AS-T2D and 65 AS-noT2D) were recruited (mean, 71 years of age [95% CI, 69, 73]; 34 [37%] women). Thirty demographically matched healthy volunteers (HVs) and 30 patients with T2D without AS (T2D controls) were controls. One month before and 6 months after AVR, cardiac PCr/ATP, adenosine stress MBF, global longitudinal strain, NT-proBNP (N-terminal pro-B-type natriuretic peptide), and 6-minute walk distance were assessed in patients with AS. T2D controls underwent identical assessments at baseline and 6-month follow-up. HVs were assessed once and did not undergo 6-minute walk testing. RESULTS: Compared with HVs, patients with AS (AS-T2D and AS-noT2D combined) showed impairment in PCr/ATP (mean [95% CI]; HVs, 2.15 [1.89, 2.34]; AS, 1.66 [1.56, 1.75]; P<0.0001) and vasodilator stress MBF (HVs, 2.11 mL min g [1.89, 2.34]; AS, 1.54 mL min g [1.41, 1.66]; P<0.0001) before AVR. Before AVR, within the AS group, patients with AS-T2D had worse PCr/ATP (AS-noT2D, 1.74 [1.62, 1.86]; AS-T2D, 1.44 [1.32, 1.56]; P=0.002) and vasodilator stress MBF (AS-noT2D, 1.67 mL min g [1.5, 1.84]; AS-T2D, 1.25 mL min g [1.22, 1.38]; P=0.001) compared with patients with AS-noT2D. Before AVR, patients with AS-T2D also had worse PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.66 [1.56, 1.75]; P=0.04) and vasodilator stress MBF (AS-T2D, 1.25 mL min g [1.10, 1.41]; T2D controls, 1.54 mL min g [1.41, 1.66]; P=0.001) compared with T2D controls at baseline. After AVR, PCr/ATP normalized in patients with AS-noT2D, whereas patients with AS-T2D showed no improvements (AS-noT2D, 2.11 [1.79, 2.43]; AS-T2D, 1.30 [1.07, 1.53]; P=0.0006). Vasodilator stress MBF improved in both AS groups after AVR, but this remained lower in patients with AS-T2D (AS-noT2D, 1.80 mL min g [1.59, 2.0]; AS-T2D, 1.48 mL min g [1.29, 1.66]; P=0.03). There were no longer differences in PCr/ATP (AS-T2D, 1.44 [1.30, 1.60]; T2D controls, 1.51 [1.34, 1.53]; P=0.12) or vasodilator stress MBF (AS-T2D, 1.48 mL min g [1.29, 1.66]; T2D controls, 1.60 mL min g [1.34, 1.86]; P=0.82) between patients with AS-T2D after AVR and T2D controls at follow-up. Whereas global longitudinal strain, 6-minute walk distance, and NT-proBNP all improved after AVR in patients with AS-noT2D, no improvement in these assessments was observed in patients with AS-T2D. CONCLUSIONS: Among patients with severe AS, those with T2D demonstrate persistent abnormalities in myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function after AVR; AVR effectively normalizes myocardial PCr/ATP, vasodilator stress MBF, and cardiac contractile function in patients without T2D

Maternal cardiac changes in women with obesity and gestational diabetes mellitus

OBJECTIVE We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics. RESEARCH DESIGN AND METHODS Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio. RESULTS Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (−20% ± 3% vs. −18% ± 3%; P = 0.008). CONCLUSIONS Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM

Cardiovascular magnetic resonance imaging and spectroscopy in clinical long-COVID-19 syndrome: a prospective case–control study

Background The underlying pathophysiology of post-coronavirus disease 2019 (long-COVID-19) syndrome remains unknown, but increased cardiometabolic demand and state of mitochondrial dysfunction have emerged as candidate mechanisms. Cardiovascular magnetic resonance (CMR) provides insight into pathophysiological mechanisms underlying cardiovascular disease and 31-phosphorus CMR spectroscopy (31P-CMRS) allows non-invasive assessment of the myocardial energetic state. The main aim of the study was to assess whether long COVID-19 syndrome is associated with abnormalities of myocardial structure, function, perfusion and energy metabolism. Methods Prospective case–control study. A total of 20 patients with a clinical diagnosis of long COVID-19 syndrome (seropositive) and no prior underlying cardiovascular disease (CVD) and 10 matching healthy controls underwent 31P-CMRS and CMR at 3T at a single time point. All patients had been symptomatic with acute COVID-19, but none required hospital admission. Results Between the long COVID-19 syndrome patients and matched contemporary healthy controls there were no differences in myocardial energetics (phosphocreatine to ATP ratio), in cardiac structure (biventricular volumes), function (biventricular ejection fractions, global longitudinal strain), tissue characterization (T1 mapping and late gadolinium enhancement) or perfusion (myocardial rest and stress blood flow, myocardial perfusion reserve). One patient with long COVID-19 syndrome showed subepicardial hyperenhancement on late gadolinium enhancement imaging compatible with prior myocarditis, but no accompanying abnormality in cardiac size, function, perfusion, extracellular volume fraction, native T1, T2 or cardiac energetics. Conclusions In this prospective case–control study, the overwhelming majority of patients with a clinical long COVID-19 syndrome with no prior CVD did not exhibit any abnormalities in myocardial energetics, structure, function, blood flow or tissue characteristics

Maternal Cardiac Changes in Women With Obesity and Gestational Diabetes Mellitus.

OBJECTIVE: We investigated if women with gestational diabetes mellitus (GDM) in the third trimester of pregnancy exhibit adverse cardiac alterations in myocardial energetics, function, or tissue characteristics. RESEARCH DESIGN AND METHODS: Thirty-eight healthy, pregnant women and 30 women with GDM were recruited. Participants underwent phosphorus MRS and cardiovascular magnetic resonance for assessment of myocardial energetics (phosphocreatine [PCr] to ATP ratio), tissue characteristics, biventricular volumes and ejection fractions, left ventricular (LV) mass, global longitudinal shortening (GLS), and mitral in-flow E-wave to A-wave ratio. RESULTS: Participants were matched for age, gestational age, and ethnicity. The following data are reported as mean ± SD. The women with GDM had higher BMI (27 ± 4 vs. 33 ± 5 kg/m2; P = 0.0001) and systolic (115 ± 11 vs. 121 ± 13 mmHg; P = 0.04) and diastolic (72 ± 7 vs. 76 ± 9 mmHg; P = 0.04) blood pressures. There was no difference in N-terminal pro-brain natriuretic peptide concentrations between the groups. The women with GDM had lower myocardial PCr to ATP ratio (2.2 ± 0.3 vs. 1.9 ± 0.4; P < 0.0001), accompanied by lower LV end-diastolic volumes (76 ± 12 vs. 67 ± 11 mL/m2; P = 0.002) and higher LV mass (90 ± 13 vs. 103 ± 18 g; P = 0.001). Although ventricular ejection fractions were similar, the GLS was reduced in women with GDM (-20% ± 3% vs. -18% ± 3%; P = 0.008). CONCLUSIONS: Despite no prior diagnosis of diabetes, women with obesity and GDM manifest impaired myocardial contractility and higher LV mass, associated with reductions in myocardial energetics in late pregnancy compared with lean women with healthy pregnancy. These findings may aid our understanding of the long-term cardiovascular risks associated with GDM