Volumetric evaluation of 99mTc-pyrophosphate SPECT/CT for transthyretin cardiac amyloidosis: Methodology and correlation with cardiac functional parameters

Background Volumetric evaluation of 99mTechnetium-pyrophosphate (99mTc-PYP) SPECT/CT is a useful method for assessing transthyretin cardiac amyloidosis (ATTR-CA). We investigated the methodology and assessed its relationship with conventional parameters. Methods and Results We retrospectively evaluated 99mTc-PYP SPECT/CT scans of 25 patients who underwent endomyocardial biopsy and/or gene testing. Fourteen (56%) patients were diagnosed with ATTR-CA. SPECT/CT images were acquired at 3 hours after injection. Total volumes of the myocardial regions where uptakes were > 1.2 and 1.4 × aortic blood pool SUVmax were evaluated and defined as cardiac pyrophosphate volume (CPV1.2 and CPV1.4). The heart-to-contralateral lung (H/CL) ratio and myocardial SUVmax were also calculated. CPV1.2 achieved the highest sensitivity and specificity in diagnosing ATTR-CA. In patients diagnosed with ATTR-CA (n = 14), CPV1.2 negatively correlated with left ventricular ejection fraction and positively correlated with left ventricular posterior wall thickness and QRS duration. The correlation was stronger in CPV1.2 than in the H/CL ratio and SUVmax. Conclusion Volumetric evaluation of 99mTc-PYP SPECT/CT may be superior to the H/CL ratio and SUVmax in assessing the disease burden of ATTR-CA. Larger studies are warranted to clarify whether volumetric measurement can assess prognosis and disease progression.

Abnormal left ventricular geometry in female collegiate swimmers

Background There is a paucity of data describing left ventricular geometry changes in female athletes. While some studies suggest that female athletes participating in dynamic sports exhibit higher prevalence of eccentric left ventricular hypertrophy (LVH) when compared to men, a recent study suggested more concentric geometry changes in female basketball athletes. We were unable to identify studies describing the left ventricular geometry of female collegiate swimmers. Objectives To describe LV geometry changes in a cohort of female collegiate swimmers. Methods We analyzed a cohort of female collegiate swimmers who had a pre-participation cardiac evaluation by 12-lead ECG and 2-dimensional echocardiography. Left ventricular (LV) geometry was assessed based on relative wall thickness (RWT) (defined as: 2 x posterior wall thickness (PWT) divided by LV end-diastolic diameter (LVEDD)) and LV mass (LVM) (Devereux's formula: LVM = [0.8 x 1.04 [(LVEDD + interventricular septum + posterior wall thickness)3 − (LVEDD)3]] + 0.6g) and was indexed to body surface area (BSA).LVH was defined as LV mass index >95 g and was defined as concentric when associated with a relative wall thickness (RWT) >0.42 and as eccentric when RWT was ≤0.42. Concentric remodeling was defined as normal LVM index and increased RWT. Results A total of 83 female collegiate swimmers were included. Their age was 18.5±0.5 years (mean ± standard deviation, SD), 74 (89.2%) were White, BSA was 1.78±0.11 m2, height 173±6.3 cm, weight 66.2±7.2 K. Their interventricular septum diameter was 0.89±0.14 cm, PWT 0.92±0.15 cm, LVEDD 4.9±0.5 cm and LV end-systolic diameter (LVESD) 3.2±0.4 cm. Left atrium diameter ranged from 2.6 to 4.3 cm (mean 3.4 cm ± 0.4 cm). Aortic root diameter ranged from 1.9 to 3.5 cm (mean 2.7±0.3 cm) (Figure 1). LVH was present in 27 swimmers (32.5%). Eccentric LVH was present in 17 athletes (20.5%), concentric hypertrophy in 10 athletes (12%), and concentric remodeling in 12 (14.5%) (Figure 2). No athletes with LVH or concentric remodeling had borderline or abnormal ECG findings based on international criteria. Only two women with normal LV geometry had abnormal ECG findings: prolonged QT interval and abnormal T wave inversion. There was a linear correlation between BSA with LVEDD, LVESD and LV mass (r=0.40, 0.35, and 0.48 with P<0.001,0.002 and <0.001, respectively). However, there was no statistically significant difference between LV geometry groups based on BSA or blood pressure. Conclusion Our data document a high incidence of eccentric hypertrophy among female collegiate swimmers. Concentric remodeling and hypertrophy were also relatively high. Differentiating physiologic from pathologic cardiac remodeling in these athletes is critical to prevent potential complications such as sudden cardiac death, arrhythmias, and other adverse outcomes. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): This work was supported in part by the American Medical Society for Sports Medicine (AMSSM) Foundation Research Grant 2016 awarded to KE, and the University of Florida REDCap uses the NIH National Center for Advancing Translational Sciences (NCATS) grant UL1 TR001427. Figure 1 Figure 2. LV geometry in female swimmers

A Study of Echocardiographic Changes in Patients with Newly Diagnosed Primary Hypothyroidism: A Cross-sectional Study

Background: Hypothyroidism is known to cause reversible cardiac dysfunction in humans. Thyroid hormone alters the cardiovascular hemodynamics. This study was performed to assess echocardiographic changes in untreated newly diagnosed primary hypothyroid states as such studies are scarce in our setting.Methods: This hospital based cross-sectional study was conducted among 71 patients with newly diagnosed primary hypothyroidism who presented to the medicine outpatient department, at Universal College of Medical Sciences and Teaching Hospital (UCMS-TH), Bhairahawa, Nepal from December 2018 to June 2020 after taking ethical clearance from institutional review committee (UCMS/IRC/212/18). Thyroid function test and echocardiography were carried out in patients under study. The data was analyzed with SPSS Version 16.Results: A total of 71 patients (52 females and 19 males) with primary hypothyroidism were enrolled for the study. Among these 58 cases were overt/clinical hypothyroidism, and 13 cases were subclinical hypothyroidism. Echocardiography was abnormal in 63.4% of cases with 43.7% showing diastolic dysfunction, 18.3% diastolic interventricular septal thickness abnormality, 8.5% diastolic left ventricular posterior wall thickness abnormality, and 8.4% pericardial effusion. Conclusion: Our study found diastolic dysfunction, diastolic interventricular septal thickness abnormality, diastolic left ventricular posterior wall thickness abnormality, and pericardial effusion as the common echocardiographic change in patients with newly diagnosed primary hypothyroidism. Therefore, our study highlights the need for cardiac evaluation of patients with primary hypothyroidism so that early intervention can be performed to improve the clinical outcome.

Leptin Attenuates Cardiac Hypertrophy in Patients with Generalized Lipodystrophy

Context Lipodystrophy syndromes are rare disorders of deficient adipose tissue, low leptin, and severe metabolic disease, affecting all adipose depots (generalized, GLD) or only some (partial, PLD). Left ventricular (LV) hypertrophy is common (especially in GLD); mechanisms may include hyperglycemia, dyslipidemia, or hyperinsulinemia. Objective Determine effects of recombinant leptin (metreleptin) on cardiac structure and function in lipodystrophy. Design/Participants/Intervention/Setting Open-label treatment study of 38 subjects (18 GLD, 20 PLD) at the National Institutes of Health before and after 1 (N=27), and 3-5y (N=23) of metreleptin. Outcome Echocardiograms, blood pressure (BP), triglycerides, A1c, HOMA-IR Results In GLD, metreleptin lowered triglycerides (median(IQR) 740(403-1239), 138(88-196), 211(136-558) mg/dL at baseline, 1y, 3-5y, P<0.0001), A1c (9.5±3.0, 6.5±1.6, 6.5±1.9%, P<0.001), and HOMA-IR (34.1(15.2-43.5), 8.7(2.4-16.0), 8.9(2.1-16.4), P<0.001). Only HOMA-IR improved in PLD (P<0.01). Systolic BP decreased in GLD but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8±1.7, 9.1±1.3, 8.3±1.7 mm, P<0.01), and LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 g, P<0.01), and increased septal e’ velocity (8.6±1.7, 10.0±2.1, 10.7±2.4 cm/s, P<0.01). Changes remained significant after adjustment for BP. In GLD, multivariate models suggested that reduced posterior wall thickness and LV mass index correlated with reduced triglycerides and increased septal e’ velocity correlated with reduced A1c. No changes in echocardiographic parameters were seen in PLD. Conclusion Metreleptin attenuated cardiac hypertrophy and improved septal e’ velocity in GLD, which may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to leptin-sufficient populations remains to be determined.

Association of sulfur content in erythrocytes with cardiovascular parameters and blood pressure

OBJECTIVE: The study aims at assessing the relationship between blood pressure, heart geometry parameters, and the erythrocyte content of sulfur, potassium, chlorine and phosphorus, in a group of patients with laboratory systolic and diastolic blood pressure (SBP, DBP) below 140 or 90 mm Hg, respectively, who were otherwise healthy and untreated. METHODS: The study group consisted of 42 adults recruited in a primary care setting. The individuals were healthy, not undergoing any therapy and free from smoking. For each individual, data were obtained on: average 24-hour SBP and DBP, left ventricle geometry, complete blood count, lipids profile, fibrinogen, hs-CRP and the erythrocyte concentration of sulfur (S), potassium (K), chlorine (Cl) and phosphorus (P). RESULTS: Multivariate regression analysis showed statistically significant relationships of diastolic posterior wall thickness (PWTd) and relative wall thickness (RWT) with the concentration ratio of sulfur and potassium (S/K) in erythrocytes: PWTd and RWT increase as the S/K ratio increases. Also, SBP was found to be positively correlated with the S/K ratio. CONCLUSIONS: The increase in sulfur content in RBCs could be an indicator of the downregulation of nitric oxide (NO) erythrocyte bioavailability exerted by endogenously produced hydrogen sulfide (H2S), and, in consequence, a marker of the development of hypertension and/or adverse changes in heart geometry.

Investigating Insulin Resistance in Pediatric Cardiomyopathy - A Pilot Study

Children with cardiomyopathy are a vulnerable population and understanding the factors that contribute to cardiac dysfunction are of great importance. At the biochemical level, energy utilization by cardiomyocytes during stress may provide insight into the progression of cardiomyopathy. There is a large body of literature that describes insulin resistance in adults with cardiomyopathy (1,2). Extensive literature on the topic in adult individuals exists however investigation in the pediatric population is sparse. The pathophysiology of disease in children and adolescents is unique. To study the role of insulin resistance in pediatric cardiomyopathy, we measured the homeostasis model assessment-estimated insulin resistance (HOMA-IR) at baseline in pre-pubertal patients (age 13-18 years old; mean 16 years old; n = 8) with either hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM). In patients with HCM, greater insulin resistance was positively correlated with greater left ventricular (LV) septal thickness (r = 0.55; p = 0.33; n = 5) and LV posterior wall thickness (r = 0.7; p = 0.19; n = 5) during diastole. As expected, insulin resistance was strongly correlated with BMI (r = 0.84; p = 0.08; n = 5) though greater BMI was not as strongly associated with LV septal thickness (r = 0.59; p = 0.3; n = 5) or posterior wall thickness (r = 0.59; p = 0.3; n = 5). In patients with DCM, insulin resistance was positively correlated with LV end diastolic volume (r = 0.59; p = 0.59; n = 3). Interestingly, there was an observed inverse association between insulin resistance and BMI in DCM (r = -0.85; p = 0.34; n =3). Though our sample population is limited, thus affecting statistical significance, results showed that there was a trend towards greater insulin resistance in patients with poorer cardiac measurements. These findings are consistent with adult literature and the proposition that cardiac dysfunction is an insulin resistant state. References: (1) Riehle C, Abel ED. Insulin Signaling and Heart Failure. Circulation research. 2016;118(7):1151-1169. (2) Shah A, Shannon RP. Insulin resistance in dilated cardiomyopathy. Reviews in cardiovascular medicine. 2003;4 Suppl 6:S50-57

Leptin Improves Cardiac Structure and Function in Patients With Generalized Lipodystrophy

Lipodystrophy (LD) syndromes are rare disorders of deficient adipose tissue and severe metabolic disease, including insulin resistance, diabetes, and hypertriglyceridemia. LD may affect all adipose depots (generalized LD, GLD) or only some depots (partial LD, PLD). Low adipose mass leads to very low leptin in GLD, and variable leptin in PL. Treatment with exogenous leptin (metreleptin) improves metabolic disease in LD, particularly GLD. Left ventricular (LV) hypertrophy is frequent in LD, especially GLD. The mechanism for hypertrophy in LD is not known and may relate to glucose or lipotoxicity. We hypothesized that metreleptin would improve cardiac abnormalities in LD, and that this would be mediated by improvements in glucose and triglycerides (TG). We analyzed echocardiograms (echo), blood pressure (BP), heart rate (HR), and metabolic parameters in 38 subjects with LD (18 GLD, 20 PLD) who were treated with metreleptin in open-label clinical studies at the National Institutes of Health. 27 had repeat echo after 1y of metreleptin (mean 1.0 ± 0.2y), and 23 after 3 to 5y (mean 3.7±0.6y). In GLD, metreleptin significantly improved metabolic disease, including reduced TG (median(IQR) 740(403–1239), 138(88–196), 211(136–558) mg/dL at baseline, 1y, & 3-5y, P<0.0001), hemoglobin A1c (9.5±3.0, 6.5±1.6, 6.5±1.9% at baseline, 1y, & 3-5y, P<0.001), and insulin resistance by HOMA-IR (34.1 (15.2–43.5), 8.7 (2.4–16.0), 8.9 (2.1–16.4), P<0.001). Only HOMA-IR improved in PLD (P<0.01). Systolic BP and HR decreased after metreleptin in GLD (BP 120±11, 117±10, 109±16 mmHg, P=0.046; HR 89±9, 82±12, 80±16 bpm, P=0.018; at baseline, 1y, 3-5y, respectively) but not PLD. Metreleptin improved cardiac parameters in patients with GLD, including reduced posterior wall thickness (9.8±1.7, 9.1±1.3, 8.3±1.7 at baseline, 1y, & 3-5y, P<0.01), LV mass (140.7±45.9, 128.7±37.9, 110.9±29.1 at baseline, 1y, & 3-5y, P<0.01), and LV mass index (88.6±22.0, 81.6±16.9, 81.6±16.9 at baseline, 1y, & 3-5y, P<0.01). Metreleptin also improved septal e’ velocity, a measure of early diastolic cardiac function, in GLD (8.6±1.7, 10.0±2.1, 10.7±2.4 at baseline, 1y, & 3-5y, P<0.01). All changes remained significant after adjustment for BP. In GLD, multivariate variable selection models suggested that changes in posterior wall thickness and LV mass index related to metreleptin-induced reductions in TG, and changes in septal e’ velocity related to metreleptin-induced reductions in hemoglobin A1c. No changes in echo parameters were seen in PLD. These findings suggest that metreleptin improves cardiac hypertrophy and diastolic function in patients with GLD, and these improvements may be mediated by reduced lipotoxicity and glucose toxicity. The applicability of these findings to a broader, leptin-sufficient population with LV hypertrophy and/or diabetic cardiomyopathy remains to be determined.

Dimensional Assessment of the Heart in Hypertrophic Cardiomyopathy Patients in Tertiary Care Hospitals

Hypertrophic cardiomyopathy (HCM) is one of the most prevalent disorders responsible for sudden cardiac death. Presentation of the symptoms varies due to the degree of thickening, and functional ability of the cardiomyocytes. The aims of the current study were to assess the clinical features, and cardiac morphology. This was a descriptive study with some analytical components. Thirty-four adult HCM patients were included within a duration of four months by patient selection checklist. After informed written consent, relevant information was noted and analyzed. Frequency distribution of phenotypes were, 56% asymmetric septal hypertrophy, 29% concentric hypertrophy, and 15% apical hypertrophy. Breathlessness and chest discomfort were present in 56% and 62% patients respectively, and higher in asymmetric septal HCM. Palpitation was very frequent in concentric HCM (90%). ECG revealed left ventricular hypertrophy in 85% of patients, and 79% of them had ST change. The interventricular septal thickness was narrower in apical type (14.80mm). The posterior wall thickness was higher in concentric HCM (19.20mm). The left atrial size was smaller in Concentric type(34.60mm).

Evaluation of Cardiovascular Variables in a Calchaquí Population in the Middle and High Mountains of Tucumán

Background: The Quilmes community includes 2,400 inhabitants of the middle and high mountains of Tucumán (1,800 to 4,000 meters above sea level). The purpose of the present study was to know their cardiovascular health status. Methods: A cross-sectional descriptive quantitative investigation was carried out in people belonging to the Quilmes community who voluntarily attended the planned evaluation on September 27-29, 2018. Results: Two hundred and two settlers were studied (125 women and 77 men; 48±1.4 years), 23% of them had hypertension (HTN); 14% were smokers; 4.9% had diabetes; 18% had dyslipidemia (DLP) and 25% usually consumed alcohol (1.0 ± 0.4 L/day). Also, 29% were overweight and 36% obese. High blood pressure (BP) was recorded in 48 individuals at the time of the study. Blood pressure decreased in the third compared to the first measurement, whereas heart rate increased in the third assessment (74±1 beats per minute vs. 77±1; p <0.01). Oxygen saturation (95.0±0.2%) was negatively correlated with age (Pearson r: -0.266; p <0.001). In individuals with normal BP, ultrasound E/ratio was higher (1.2±0.0) and left ventricular posterior wall thickness was lower (8.5±0.5 mm) than in those with elevated BP (0.92±0.1 and 9.0±0.3, respectively, p <0.001). Twenty-four percent of individuals had atherosclerotic plaques and 120 had DLP. Conclusions: The Quilmes population presents a prevalence of cardiovascular risk factors similar to that of urban centers, which could lead to an increase in cardiovascular morbidity and mortality in the coming years

Relationship of left ventricular and atrial dimensions with moderate to severe left ventricular diastolic dysfunction (grade II and above)

Introduction: Left ventricular diastolic dysfunction (DD) is an entity in which the ventricle fails to fill up properly due to impaired ventricular relaxation and/or decreased compliance. The diagnosis of diastolic dysfunction is based on a variety of parameters in doppler echocardiograpy. However, some parameters like interventricular septal thickness in diastole (IVSd), posterior wall thickness in diastole (PWd), left ventricular internal end diastolic and systolic diameters (LVIDD and LVISD) along with left atrial diameters (LAD) have yet to be evaluated for the diagnostic workup of DD. Methods: A case control study was done in the cardiology department from patient records from 2016 to 2018. Patients were diagnosed as diastolic dysfunction grade II and above by doppler echocardiography. IVSd, PWd, LVIDD, LAD, LVISD were obtained through 2-D echocardiography. Results: Patients with DD had greater LAD, IVSd and PWd and decreased LVIDD and LVISD as compared to control group. Overall, IVSD was the most significant predictor (OR 1.52 95%CI 1.35-1.71) of DD followed by PWd and LAD. Similarly, LAD, IVSd and PWd had higher sensitivity and specificity than LVIDD and LVIDS. Conclusion: IVSd, LAD and PWd showed significant performance in the diagnosis of diastolic dysfunction and hence can be used as a screening and diagnostic tool in diastolic dysfunction of grade ll and above. Keywords: Heart failure; diastolic; echocardiography; left ventricle.