Concentric Left Ventricular Hypertrophy Research Articles

Association of arterial stiffness, N-terminal pro-brain natriuretic peptide, insulin resistance, and left ventricular diastolic dysfunction with diabetic cardiac autonomic neuropathy

Aim: To investigate the changes of insulin resistance (IR), parameters of arterial stiffness, concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP), and echocardiographic parameters in patients with cardiac autonomic neuropathy (CAN) and type 2 diabetes mellitus (T2D). Methods: This study recruited 44 patients with T2D (19 patients without CAN and 25 patients with CAN) and 15 healthy volunteers. Arterial stiffness, immunoreactive insulin, homeostasis model assessment IR, NT-proBNP parameters, and echocardiographic examination were assessed. Results: Development of CAN is associated with increase in NT-proBNP levels, IR parameters, and arterial stiffening. Among patients with CAN, arterial stiffness parameters were considered as high. We found out that among patients of this group, the value of brachial augmentation index was normal in 52%, elevated in 40%, and pathological in 8%; pulse wave velocity was normal in 16%, elevated in 52%, and pathological in 32% of cases. Obtained results showed that development of CAN is accompanied by more pronounced left ventricular diastolic dysfunction and by formation of left ventricular hypertrophy (LVH), mostly by concentric type. Among patients of this group concentric LVH was diagnosed among 76 % and eccentric LVH among 16% of persons. Multiple regression analysis, after controlling for age, sex, diabetes duration, blood pressure, HbA1c, and left ventricular mass index, showed an independent association of heart rate response to deep breathing with pulse wave velocity (P < 0.001). Conclusion: Development of CAN is associated with increased IR parameters, increased levels of NT-proBNP, arterial stiffening, left ventricular diastolic dysfunction, and formation of LVH, mostly by concentric type.

Hypertension and Type 2 Diabetes Mellitus Secondary to Acromegaly, A Rare Endocrine Disease: A Case Report

Background: Acromegaly is a rare endocrine disorder that emanates from excessive release of growth hormone leading to the production of insulin-like growth factor I (IGF-I) which causes most of the clinical features of the disease. Methods: A case report study of Acromegaly that presented in the Niger Delta University Teaching Hospital, Bayelsa State, Nigeria. Results: Random Blood Sugar -25mmol/dl, Fasting Blood Sugar-17.8mmol/dl, HbAIc-13.0%, Prolactin-6.64ng/ml, Cortisol- 12.5ug/dl, FSH-0.20Miu/ml, Testosterone-0.35ng/ml, TSH-1.26Uiu/ml, Growth Hormone; Insulin-like Growth Factor 1->1600ng (115-307). Her Blood Pressure was 180/120 mmHg. Heart sounds were S4, 1 and 2.Echocardiogram revealed concentric LVH, no regional wall motion abnormality. Perimetry showed inferior nasal defect of the Left eye. Conclusion: This case report reiterates the need for more health education and public enlightenment on clinical entities such as Acromegaly, with an emphasis on debunking some of the myths and social stigma associated with this chronic progressive disfiguring and disabling disease in our environment.

GENDER FEATURES OF STRUCTURAL-GEOMETRIC REMODELING OF THE LEFT VENTRICLE IN PATIENTS WITH MYOCARDIAL INFARCTION WITHOUT ELEVATION OF ST SEGMENT

Recently, there has been a tendency to increase the incidence of myocardial infarction without elevation of the ST segment, which, according to some data, accounts for about half of all registered MI. The main problem with this type of infarction is that the long-term prognosis in these patients remains unsatisfactory, and mortality one year after the catastrophe is equal to or even higher than mortality from ST-segment elevation myocardial infarction, which encourages continued predictors of unfavorable prognosis.
 Objective: to determine the gender characteristics of the structural and geometric remodeling of the left ventricle in patients with myocardial infarction without ST segment elevation.
 Materials and methods. We conducted a comprehensive study of 200 patients with acute myocardial infarction without ST-segment elevation (NSTEMI) aged 38 to 80 (mean 62.0 ± 0.71, median 62 and interquartile range 55 and 70). The structural and functional state of the myocardium and types of left ventricular remodeling according to transthoracic echocardiography were studied.
 Results. Analysis of the obtained data shows that echocardiographic parameters in patients with NSTEMI depending on gender did not reveal significant differences between different groups. The exception was the size of the right atrium, which was significantly higher in the group of men compared to women with comparable values of the size of the right ventricle and the ratio of the size of the left to the right atrium. Analysis of the nature of structural and geometric remodeling of the left ventricle in general by groups showed that almost half of the subjects registered concentric hypertrophy of the left ventricle. Concentric left ventricle remodeling was observed in one third of patients and in other patients - normal geometry and eccentric left ventricle hypertrophy. Thus, it was found that concentric models of left ventricle – concentric hypertrophy and concentric remodeling – were registered in the vast majority of patients with NSTEMI. The latter can be explained by a significant proportion of hypertension which was identified by us in most patients and, of course, contributed to the development of concentric models of left ventricle.
 Analysis of the nature of structural and geometric remodeling of the left ventricle depending on gender showed that in the group of men, compared with women, there was a significant increase in the incidence of concentric remodeling. At the same time, in women, compared with men, there was a significant increase in cases of more severe types of structural remodeling - concentric and eccentric hypertrophy.
 Thus, we found that gender differences in echocardiographic parameters in patients with NSTEMI relate exclusively to indicators of structural and geometric remodeling of the left ventricle. Signs of concentric and eccentric left ventricular hypertrophy predominate in women, and indicators of normal geometry and concentric left ventricular remodeling in men. This distribution of types of remodeling indicates a more severe course and unfavorable prognosis of NSTEMI in women.

Longitudinal systolic dysfunction in hypertensive cardiomyopathy with normal ejection fraction

The left ventricle (LV) journey in their transition from hypertrophy to heart failure is marked by many subcellular events partially understood yet. The moment in which the structural abnormalities reach the umbral to induce myocardial dysfunction remains elusive. To evaluate the anatomic-functional relationship between LV wall thickness and longitudinal systolic dysfunction. We prospectively performed clinical assessment and transthoracic echocardiogram on healthy individuals and hypertensive patients with left ventricle ejection fraction (LVEF) ≥50% and absence of heart failure symptoms. A total of 226 patients and 101 healthy individuals were recruited. The distribution for sex was similar between groups. The mean age was 67±13 years old in the patients, and 44% had concentric LV hypertrophy. LVEF was identical in both groups (63±6%); in contrast, global longitudinal strain (GLS) (-18.8±2.5%vs -20.4±2%) and mitral annulus plane systolic excursion (MAPSE) (13.8±2.8vs 15.5±2mm) were lower. ROC curve optimally classified decreased GLS with LV septum thickness ≥13mm and decreased MAPSE with thickness ≥14mm. Multivariable logistic regression found that LV septum thickness is the only variable associated with longitudinal systolic dysfunction (OR=1.1, CI95% = 1.05 - 1.15, P=0.001, R squared=.38). A progressive increase in LV wall thickness due to myocyte hypertrophy and interstitial expansion is associated with LV systolic longitudinal dysfunction. Patients with moderate or severe ventricular hypertrophy (septum ≥13mm) had longitudinal systolic dysfunction, GLS decreases with minor structural change than MAPSE, and LVEF is insensitive in detecting longitudinal myocardial dysfunction in patients with hypertension.

Prediction of Adverse Perinatal Outcomes and Preeclampsia in Pregnant Women with Chronic Arterial Hypertension

The objective of this study was to determine predictors and develop a prognostic model for preeclampsia (PE) and adverse perinatal outcomes in pregnant women with chronic arterial hypertension (CAH). Methods and Results: The study cohort included pregnant women (n=376) with hypertensive disorders: Group 1 –pregnant women with CAH (n=134), Group 2 – with PE on the background of CAH (n=242). Healthy pregnant women made up the control group (n=34). The diagnosis of pregnant women with CAH was made on the basis of existing national and foreign recommendations that an increase in SBP ≥140 mmHg and/or DBP ≥90 mmHg indicates CAH. All patients underwent the following examinations: a survey on a special questionnaire; an anthropometric examination; physical examination; an assessment of the content of uric acid (UA) in the blood serum and microalbuminuria (MAU) in the urine at 6-8 and 16-17 weeks of pregnancy; 12-lead ECG, echocardiography, 24-hour ambulatory blood pressure monitoring, sonography of the uterus, fetus, and placenta at 6-8 and 16-18 weeks. It was found that an inappropriate left ventricular mass (LVM) in pregnant women with CAH, a certain “phenotype” of 24-hour ABPM and indicators of metabolic disorders demonstrate the systemic nature of organ damage and appear to be a predictor of adverse perinatal outcomes and the development of PE. The revealed changes in the LV structure, which are more significant in PE on the background of CAH, suggest the association of concentric left ventricular hypertrophy and disorders of uteroplacental blood flow. Detecting abnormal blood flow from early pregnancy will reduce not only perinatal morbidity and premature birth, but also the probability of organ (LV myocardium, kidney) damage in women with CAH. To predict the risks of adverse perinatal outcomes in pregnant women with CAH and PE, a number of factors were identified that have a statistically significant relationship with the studied complications. The developed model makes it possible to predict the probability of PE and unfavorable perinatal outcomes in pregnant women suffering from CAH with high efficiency (91.1%).

751 Quantitative changes in intracardiac vortices between patients with different ventricular geometry

Abstract Aims Over the past decades growing evidence have demonstrated the promising role of intracardiac fluid-dynamics in evaluating cardiac performance. To investigate quantitative changes in vortices parameters in patients with different ventricular geometry. Methods and results We enrolled 50 consecutive patients with one of the following: LV concentric hypertrophy (CH), eccentric hypertrophy (EH), concentric remodelling, and normal LV geometry (CTRL). They underwent a complete echocardiographic examination with intracardiac fluid-dynamic analysis by Color Vector Flow Mapping (Hyperdoppler). The following parameters were obtained: vortex area (VA); vortex length (VL); and vortex depth (VD). Bland Altman Plot has been used to assess intra and inter-observer variability. Mean VD was higher in CR, CH, and EH compared to CTRL (P = 0.013, P = 0.001, and P = 0.022, respectively). Moreover, CH showed higher VL (P = 0.006) and larger VA (P = 0.012) compared to CTRL. A similar trend was noticed in EH patients, despite did not reach statistical significance (P = 0.21 and P = 0.07 for VA and VL, respectively). No significative differences in vortices parameters have been observed between CH and EH. Conclusions This is the first study providing quantitative echocardiographic parameters of vortex location and morphology in different LV geometries. Quantitative fluid-dynamic assessment was feasible and reliable in the whole population.

228 Management and treatment of an hypertrophic cardiomyopathy phenotype

Abstract Methods and results We are presenting the case of a 75-year-old man who was received in our Cardiomyopathy unit in 1986 with echocardiography showing evidence of left ventricular concentric hypertrophy and a subsequent diagnosis of a sarcomeric hypertrophic cardiomyopathy. During the follow-up, a progressive increase in mid-ventricular pressure gradient was reported and increasing pulmonary arterial pressure, even though the patient was asymptomatic. In 2013, the patient was hospitalized after a resuscitated cardiac arrest due to VF. The coronary angiogram did not show any significant coronary obstructions. The echocardiography showed a systolic anterior motion (SAM) of the mitral valve causing a dynamic pressure gradient in the left ventricular outflow tract reaching 90 mmHg and pulmonary hypertension (PAPs 60 mmHg). A double-chamber ICD was implanted as a secondary prevention of SCD and after a discussion with the Heart-Team, a surgical myectomy with the Morrow technique was performed on the patient. A total of 16 grams of myocardium was removed from the basal interventricular septum, three II order chordae tendineae were dissected from the AML and a mitral valve repair was performed on the patient. The myocardium was reported to show the typical aspects of infiltration; for this reason, a wide genetic analysis was performed which led to the diagnosis of Anderson–Fabry disease (a hemizygous GLA mutation and a homozygous MYBPC3 mutation). Therefore, specific enzymatic therapy was started. The genetic analysis was extended to the patient’s relatives leading to the that the patient’s brother and daughter were both carriers of the mutation. Starting in 2019, the patient began to develop symptoms of cardiac failure (mainly dyspnoea). An echocardiographic investigation showed a moderate to severe aortic regurgitation, a moderate mitral regurgitation, moderate left ventricular dilation, and pulmonary hypertension. The patient’s case was submitted to the Heart-Team’s discussion: due to the patient’s age and clinical conditions, heart transplantation was rejected and medical therapy was decided to be the best option. In 2021 the patient presented with worsening of clinical conditions including dyspnoea during daily activities (NYHA III). An echographic investigation found severe mitral regurgitation with a dilated and hypokinetic LV (EF 30%). The patient was hospitalized for decompensated HF: the coronary angiography did not show CAD and the cardiac catheterization showed low cardiac output without high vascular pulmonary resistances. After the Heart-Team re-evaluation, we decided to perform a percutaneous correction of the mitral regurgitation and in July 2021 Mitraclip implantation was performed on the patient without peri- and post-procedural complications. At the 3-month evaluation the patient was in better clinical conditions with improvement in his functional status (NYHA II). This patient is now continuing outpatient follow-up and we are considering the possibility of a future transcatheter correction of aortic valve regurgitation. Conclusions we submitted this clinical report with the aim to show how, thanks to the development of increasingly advanced diagnostic and therapeutic tools, it is nowadays possible to manage these complex phenotypes and their complications.

Single-Dose Cold Modified Bretschneider Solution for Myocardial Protection in the Surgical Treatment of Patients with Aortic Valve Stenosis and Left Ventricular Hypertrophy

Summary Aortic valve stenosis (AS) is predominantly caused by degenerative calcification in patients over 70 years. It obstructs the left ventricular outflow tract. The result is concentric left ventricular hypertrophy (LVH) wall stress and ischemia-induced myocardial fibrosis. [1] According to the European Association of Cardiothoracic Surgery, all high-grade AS patients are indicated for Aortic valve intervention [2]. One of the most recommendable methods for myocardial protection during surgical aortic valve replacement is antegrade delivery of cold crystalloid cardioplegia. Our retrospective study included 173 operated patients with AS and LVH. We observed the MB fraction of the enzyme creatine phosphokinase (CPK-MB) as a postoperative marker for myocardial hypoprotection in different patients. Our results showed that a single dose of modified Bretschnaider solution provided safe and long enough myocardial protection during conventional and minimally invasive aortic valve replacement in patients with AS and LVH [3].

C89. Simultaneous Aortic Stenosis (AS) and Pulmonary Stenosis (PS) in A Middle-Aged Man: A Rare Case Report

Abstract Background Combined valvular lesions is very rare. Only 16 cases of combined valvular stenosis of the aortic and pulmonary valves have been reported. Failure to recognize and adequately correct both lesions may be catastrophic for the patient. Case Illustration A 38-year-old male came to the outpatient department with shortness of breath, fatigue, and swollen ankles. He had a short posture, broad forehead, bitemporal narrowing, broad nasal tip, long philtrum, wide mouth, and large earlobes. Cardiac examination revealed systolic murmurs over the pulmonary valve and at the aortic valve radiating to the apex (galliverdin phenomenon), rales in both lungs, and bilateral ankle edema. Electrocardiogram revealed sinus rhythm, extreme axis, RA enlargement, RBBB, and bifascicular block. Chest radiograph showed cardiomegaly, pulmonary edema, and left pleural effusion. Echocardiography demonstrated a dilated LA and concentric LVH with good LV function, HF/HG severe AS, a bicuspid aortic valve causing moderate aortic regurgitation, mild mitral regurgitation, mild tricuspid regurgitation, and severe valvular or supravalvular PS with RV hypertrophy. The patient was administered diuretics, a beta blocker, and an anti-platelet. Discussion Most patients with combined aortic and pulmonary obstruction at sub-valvular level have hypertrophic cardiomyopathy. Cases with both aortic and pulmonary valve stenoses are exceedingly rare. The age of presentation ranges from neonate to 55 years. It is more common in males. Most patients present with murmur since birth, dyspnea, and fatigue. Our patient is suspected to have Williams syndrome based on the physical appearance and cardiac examination findings.

C89. Simultaneous Aortic Stenosis (AS) and Pulmonary Stenosis (PS) in A Middle-Aged Man: A Rare Case Report

Abstract Background Combined valvular lesions is very rare. Only 16 cases of combined valvular stenosis of the aortic and pulmonary valves have been reported. Failure to recognize and adequately correct both lesions may be catastrophic for the patient. Case Illustration A 38-year-old male came to the outpatient department with shortness of breath, fatigue, and swollen ankles. He had a short posture, broad forehead, bitemporal narrowing, broad nasal tip, long philtrum, wide mouth, and large earlobes. Cardiac examination revealed systolic murmurs over the pulmonary valve and at the aortic valve radiating to the apex (galliverdin phenomenon), rales in both lungs, and bilateral ankle edema. Electrocardiogram revealed sinus rhythm, extreme axis, RA enlargement, RBBB, and bifascicular block. Chest radiograph showed cardiomegaly, pulmonary edema, and left pleural effusion. Echocardiography demonstrated a dilated LA and concentric LVH with good LV function, HF/HG severe AS, a bicuspid aortic valve causing moderate aortic regurgitation, mild mitral regurgitation, mild tricuspid regurgitation, and severe valvular or supravalvular PS with RV hypertrophy. The patient was administered diuretics, a beta blocker, and an anti-platelet. Discussion Most patients with combined aortic and pulmonary obstruction at sub-valvular level have hypertrophic cardiomyopathy. Cases with both aortic and pulmonary valve stenoses are exceedingly rare. The age of presentation ranges from neonate to 55 years. It is more common in males. Most patients present with murmur since birth, dyspnea, and fatigue. Our patient is suspected to have Williams syndrome based on the physical appearance and cardiac examination findings.

C3. A case of extreme discrepancy between office and ambulatory blood pressure: is it true uncontrolled hypertension?

Abstract Background White coat uncontrolled hypertension (WCUH), defined as drug-treated hypertension but with increased blood pressure in the office and normal ambulatory blood pressure, should be assessed in patients with uncontrolled hypertension to prevent overtreatment. We report a case of an extreme WCUH found by ambulatory blood pressure monitoring (ABPM). Case Summary A 66-year-old woman was a regular patient in Cardiology Outpatient Clinic, Indonesian Army Central Hospital Gatot Soebroto with uncontrolled hypertension, CAD post-PCI, and insulin-dependent type 2 diabetes mellitus. The patient was overweight (BMI was 24.56 kg/m2) with dyslipidemia and uncontrolled blood glucose. Despite aggressive treatment with ARB, CCB, beta-blockers, diuretic, and clonidine, the patient had persistent hypertension with mean office systolic blood pressure >160/90 mmHg. Echocardiography showed concentric left ventricular hypertrophy. ABPM result found extreme variability of blood pressure with the average 24-hour blood pressure of 93.6/59 mmHg (mean daytime blood pressure was 90/55 mmHg and mean night-time blood pressure was 98.7/65.2 mmHg), intermittent hypotension, and reverse dipper pattern. The blood pressure once dropped to the lowest point of 69/44 mmHg, and the highest was 211/186 mmHg. Based on this result, we classified the patient’s condition as WCUH and adjusted the antihypertensive regiment. Discussion This case emphasizes the need to evaluate the presence of WCUH by ABPM in patients with uncontrolled hypertension so antihypertensive drugs could be adjusted accordingly and prevent hypotension.

C3. A case of extreme discrepancy between office and ambulatory blood pressure: is it true uncontrolled hypertension?

Abstract Background White coat uncontrolled hypertension (WCUH), defined as drug-treated hypertension but with increased blood pressure in the office and normal ambulatory blood pressure, should be assessed in patients with uncontrolled hypertension to prevent overtreatment. We report a case of an extreme WCUH found by ambulatory blood pressure monitoring (ABPM). Case Summary A 66-year-old woman was a regular patient in Cardiology Outpatient Clinic, Indonesian Army Central Hospital Gatot Soebroto with uncontrolled hypertension, CAD post-PCI, and insulin-dependent type 2 diabetes mellitus. The patient was overweight (BMI was 24.56 kg/m2) with dyslipidemia and uncontrolled blood glucose. Despite aggressive treatment with ARB, CCB, beta-blockers, diuretic, and clonidine, the patient had persistent hypertension with mean office systolic blood pressure >160/90 mmHg. Echocardiography showed concentric left ventricular hypertrophy. ABPM result found extreme variability of blood pressure with the average 24-hour blood pressure of 93.6/59 mmHg (mean daytime blood pressure was 90/55 mmHg and mean night-time blood pressure was 98.7/65.2 mmHg), intermittent hypotension, and reverse dipper pattern. The blood pressure once dropped to the lowest point of 69/44 mmHg, and the highest was 211/186 mmHg. Based on this result, we classified the patient’s condition as WCUH and adjusted the antihypertensive regiment. Discussion This case emphasizes the need to evaluate the presence of WCUH by ABPM in patients with uncontrolled hypertension so antihypertensive drugs could be adjusted accordingly and prevent hypotension.

Abstract 13208: Deletion of the Type I Interleukin-1 Receptor Prevents the Development of Cardiomyopathy Associated With Aging in Mice

Background: Aging is associated with metabolic and structural changes causing heart failure with preserved ejection fraction (HFpEF). Interleukin-1 (IL-1) is a pro-inflammatory cytokine involved in aging-related inflammation. We sought to determine whether IL-1 mediates aging-related changes in the heart as seen in HFpEF. Hypothesis: We hypothesize that mice with genetic deletion of IL-1RI, not responsive to IL-1β, would be protected from age-associated cardiac dysfunction. Methods: We studied age-matched young (4-month-old), middle-aged (14-month-old) and old (23-month-old) wild-type (WT) C57BL/6J and IL-1 receptor type I deficient (IL1RI-KO) male mice. Echocardiography was used to left ventricular (LV) dimensions and systolic/diastolic function, and a pressure-transducer was used to measure the LV end-diastolic pressure. Picrosirius red stain was used to assess for myocardial interstitial fibrosis (MIF) at pathology. Results: WT and IL-1RIKO mice showed a normal cardiac phenotype at young age, without any differences in between the two groups. With aging, the WT mice developed LV concentric hypertrophy (as measured by a significant increase in LV mass [+42%, P<0.01] and relative wall thickness [+34%, P<0.01]), whereas the aging IL-1RI-KO mice did not (Figure 1a,b). With aging the WT mice also developed diastolic dysfunction (as measured by a significant increase in isovolumetric relaxation time [+148%, P<0.01] and a significantly higher LV end diastolic pressure [+174%, P<0.01]), whereas the aging IL1RI-KO did not (Figure 1c,d). With aging WT mice showed a significant increase in MIF (+124%, P<0.01) at cardiac pathology, whereas the aging IL-1RI-KO did not (Figure 1e). Conclusions: Genetically-modified mice lacking the IL-1RI receptor, not responsive to IL-1, are protected from aging-related LV hypertrophy, fibrosis and diastolic dysfunction. These data support a central role of IL-1 in the pathophysiology of aging-related HFpEF.

Abstract 10713: Long-Term Impact of Alcohol Septal Ablation on Left Ventricular Remodeling and Diastolic Function: Retrospective Echocardiographic Assessment

Introduction: Alcohol septal ablation (ASA) is a percutaneous procedure for patients with refractory hypertrophic obstructive cardiomyopathy (HOCM). Asymmetric septal hypertrophy (ASH) and systolic anterior motion of the mitral valve (SAM) results in a dynamic left ventricular outflow tract gradient (LVOTG). LVOTG leads to concentric left ventricular hypertrophy and diastolic dysfunction. Hypothesis: We tested the hypothesis that patients who underwent ASA for treatment of HOCM would experience left ventricular remodeling and long-term improvement in diastolic function. Methods: Using a patient database maintained internally we analyzed the echocardiograms of 96 patients (36:60 M:F)(Age=60.5±13.2 years) who underwent successful ASA and had a follow-up echocardiogram at least 270 days following the procedure. Parameters used to describe diastology included interventricular septal thickness (IVSd), LV mass index (LVd mass index), LV diastolic internal diameter (LVIDd), LV end diastolic volume index (LVEDVi), left atrial end systolic volume index (LAESVi), early and late velocities across the mitral valve (MV E and A, respectively), and the MV E/A ratio. A paired t-test was used to compare baseline and follow-up echocardiogram values within individual subjects. Results: The time between ASA and follow-up echocardiogram was 653.9±350.4 days (mean±SD). At follow-up, the resting and provoked gradients were significantly reduced. Baseline and follow-up echocardiogram values were compared, revealing a significant difference in IVSd, LVPWd, LVd mass index, LVEDVi, LAESVi, MV E velocity, MV A velocity and MV E/A ratio. (Figure 1) Conclusions: Alcohol septal ablation induces significant regression of left ventricular hypertrophy and improvement in diastolic function. These changes likely contribute to long-term symptomatic improvement in patients who undergo alcohol septal ablation for treatment of hypertrophic obstructive cardiomyopathy.

Abstract 9980: Cardio-Omentopexy Requires a Cardioprotective Innate Immune Response to Promote Myocardial Angiogenesis

Introduction: The greater omentum is replete with angiogenic factors and macrophages. Cardio-omentopexy (COP), wherein the pedicled greater omentum is applied onto ischemic or pressure-overloaded hearts, has been shown to be protective in both humans and animals. However, the protective mechanisms of COP remain unclear. Hypothesis: We hypothesized that COP protects the heart against pressure overload-induced cardiac hypertrophy and dysfunction via a macrophage-dependent mechanism of myocardial angiogenesis. Methods: C57BL/6 mice underwent transverse aortic constriction (TAC) for 6 weeks followed by COP for 8 weeks. Cardiac geometry and function were evaluated using echocardiography (n=12-13 mice/group). Histochemical analyses quantified cardiomyocyte size, fibrosis, microvessel density, and macrophages. Flow cytometry was performed to analyze neutrophil/monocyte/macrophage populations. Gene expression array was also performed. A group of mice receiving both TAC and COP were intraperitoneally injected with clodronate-liposomes (5 mg/kg every three days for 8 weeks) starting on day 3 after COP. Results: TAC produced concentric left ventricular hypertrophy, reduced mitral E/A ratio, increased cardiomyocyte size, and myocardial fibrosis in the mice undergoing sham COP surgery (TAC + /COP - ). These maladaptive effects of TAC were abrogated by COP (TAC + /COP + ). Myocardial microvessel density was elevated in TAC + /COP + mice. Gene array analysis showed activation of angiogenesis gene networks by COP. Flow cytometry revealed that COP resulted in the accumulation of cardiac MHCII lo Lyve1+TimD4+ resident macrophages at the omental-cardiac interface. Moreover, the depletion of macrophages with clodronate-liposomes (Clo + /TAC + /COP + ) resulted in the failure of COP to prevent left ventricular hypertrophy, enhance mitral E/A ratio, decrease cardiomyocyte size and myocardial fibrosis, and promote angiogenesis. Conclusions: COP protects the pressure-overloaded left ventricle from hypertrophy and dysfunction, with associated angiogenesis. Cardiac resident macrophages accumulate near COP, and macrophage depletion eliminates the benefits of COP. These studies support a novel macrophage-dependent effector function of COP.

Abstract 13471: HFpEF in Spontaneously Obese Mice Due to Genomic Rearrangement in Non-Coding Region of Chromosome 1

Background: Obesity is the most common comorbidity and risk factor for heart failure (HF) in patients with preserved ejection fraction (HFpEF), a subclass containing more than 50% of HF cases. However, effective treatment of HFpEF remains scarce due to the incomplete understanding of the mechanisms. Methods: A mouse line (C57/B6J) of Floxed-stop Overexpression of IF1 (FEI) was generated and maintained for Cre-mediated conditional IF1 overexpression. We observed that severe obesity became a fixed phenotype in inbred FEI mice after inbreeding for 5-6 generations. Targeted-Locus-Amplification (TLA) analyses revealed that FEI inbreeding triggered a genomic rearrangement in a non-coding region of chromosome 1. A heterozygous line with genotype and phenotype fixation was obtained via outbreeding with wild type mice. In the present study, we focus on assessing the cardiac phenotype of FEI mice using echocardiography, histology, and exercise tolerance tests. Results: The early onset of obesity was consistent in the heterozygotes of obese FEI mice with increased peripheral fats and circulating tissue lipids, as well as reduced systemic metabolic rates. FEI mice also exhibited increased food intake, fasting blood glucose, insulin, and leptin with impaired glucose/insulin tolerance. Echocardiography revealed that the FEI mice developed concentric left ventricular hypertrophy with preserved ejection fraction. However, E/A ratio results from Doppler flow measurement at mitral valve suggest diastolic dysfunction in the FEI mice. Heart weight to tibial length ratio was significantly increased in FEI compared with WT mice. H&E and Trichrome blue staining on heart sections exhibited increased cardiomyocyte hypertrophy and cardiac fibrosis. Treadmill exercise tolerance test revealed a significantly decreased exercise tolerance in FEI mice. Conclusions: We conclude that the cardiac phenotypes in the obese FEI mice closely recapitulate obese patients who suffer from HFpEF. Thus, further studies on these mice should yield novel and translational insight into the molecular and metabolic mechanisms underlying the HFpEF development, leading to improved treatments.

Abstract 10016: Potential of Stress T1 Mapping for Detection of Microvascular Dysfunction Without Contrast Agents

Introduction: Ischemia of hypertrophic myocardium due to microvascular dysfunction is related to worse prognosis in hypertrophic cardiomyopathy (HCM). Stress T1 mapping is a novel cardiac magnetic resonance (CMR) method without contrast agents to be able to assess myocardial blood flow. Hypothesis: We assessed the hypothesis that stress T1 mapping can detect microvascular dysfunction in HCM patients. Methods: Forty-one consecutive subjects without history of coronary artery disease (mean age : 60±3 years, 25 HCM patients, 10 concentric left ventricular hypertrophy (LVH) patients and 6 control subjects) underwent CMR at 3T including cine imaging, rest and adenosine stress T1 mapping, and late gadolinium enhancement (LGE). Native and stress T1 values were measured as an averaged T1 values in the septum of 3 short-axis slices of base-to-apex left ventricle myocardium and T1 reactivity (ΔT1) was calculated as follows: ΔT1 (%) = (T1stress - T1rest)/T1rest х 100. Thirteen HCM patients underwent phase-contrast imaging of coronary sinus flow during rest and adenosine stress to assess coronary flow reserve (CFR). Results: Native T1 values in HCM patients (1271±12ms) showed no significant differences compared with LVH (1225±13ms, p=0.0877) and control subjects (1243±8ms, p=0.534), but ΔT1 in HCM patients (4.00±0.36%) was significantly lower than that in control subjects (5.97±0.41%, p=0.0272), but not in LVH patients (4.95±0.29%, p=0.265, Figure 1). In HCM patients, native T1 values and ΔT1 showed no significant differences between LGE-positive (n=19) and LGE-negative (n=6) groups (native T1: 1274±15ms vs. 1260±20ms, p=0.632, ΔT1: 4.55±0.79% vs. 3.82±0.41%, p=0.394). A moderate positive correlation between ΔT1 and CFR was seen (β=0.697, p=0.0398). Conclusions: T1 reactivity (ΔT1) was reduced in HCM patients compared to control subjects. Stress T1 mapping is a promising CMR method for the assessment of microvascular dysfunction without contrast agents.

Abstract 17189: Radiation-induced Accelerated Multi-valve Disease In A Patient With Subaortic Membrane

A 69-year-old woman with history of right breast cancer status post lumpectomy and radiation (4.2 cGy) 18 months prior, presented with progressive NYHA class III dyspnea. TTE obtained prior to her cancer diagnosis was notable for normal LV size and wall thickness, a subaortic membrane with systolic mean Doppler gradient of 21 mmHg and a mildly thickened mitral valve without significant stenosis or regurgitation. On presentation, TTE was notable for severely increased concentric LV wall thickness (LV mass index 140 g/m 2 ), preserved ejection fraction, increased RV wall thickness, subaortic stenosis with systolic mean Doppler gradient 35 mmHg, moderate-severe aortic regurgitation, thickened mitral valve with posterior leaflet tethering and anterior leaflet override causing severe mitral regurgitation and moderate mitral stenosis (valve area 1.7 cm 2 by pressure half-time). She underwent a surgical intervention with septal myectomy, subaortic membrane resection, aortic root reconstruction, aortic and mitral valve replacement with bioprostheses. She did well post-operatively and had complete resolution of symptoms following cardiac rehabilitation. Radiation-induced valvular heart disease is linked to the total dose of radiation, use of sequential chemotherapy and time since irradiation, with a typical latency of 10-20 years. However, there is paucity of data regarding the influence of these variables in patients with pre-existing valve disease. This case illustrates dramatic acceleration of underlying aortic and mitral valve pathology in a patient with a subaortic membrane, 18 months after radiation. We also noted development of significant concentric LV hypertrophy that was disproportionate to the degree of obstruction across the sub-aortic membrane. Potential candidates for radiation therapy must be carefully screened for pre-existing valve disease, which should warrant increased vigilance and early screening for progressive valve disease.

Abstract 16643: Pacemaker For First Degree AV Block Without Bradycardia: Pseudo-pacemaker Syndrome

Case Presentation: An 86 year old man underwent PCI of distal LAD for severe single vessel coronary artery disease identified after a high risk pharmacologic nuclear stress test (evaluation of exertional fatigue prior to abdominal aortic aneurysm surgical repair). ECHO was consistent with preserved LVEF (60-65%), moderate concentric LVH and mild left atrial enlargement. Less than a week after PCI, he presented to the emergency department for NYHA III dyspnea and fatigue. The patient was not taking any negative chronotropic medications. CT angiography of the chest excluded pulmonary edema, pneumonia and pulmonary embolism; repeat limited ECHO was unchanged. EKG showed first degree AV block (PR 400ms, figure 1). Severely prolonged PR interval with otherwise-unexplained exertional symptoms raised suspicion for pseudo-pacemaker syndrome. In the absence of an alternative cause of declining exertional tolerance, a dual chamber pacemaker with short programmed AV delay (<200ms) was implanted. The patient reported resolution of exertional fatigue and dyspnea on one-month followup. Discussion: Pseudo-pacemaker syndrome is a rare, infrequently reported, complication of first degree AV block with severely prolonged PR>300ms. P-wave at the end of the preceding T-wave suggests AV dyssynchrony (arrowhead, figure 1). Left atrial contraction against a closed mitral valve led to loss of atrial contribution to cardiac output, and elevated left atrial pressure. These changes, accentuated by physiologic increase in heart rate on exertion, most likely caused symptoms in this patient. It is interesting that AV dyssynchrony in pacemaker syndrome is caused by the pacemaker (VVI pacing) whereas the AV dyssynchrony in pseudo-pacemaker syndrome from severely prolonged PR interval is treated with a pacemaker. In the appropriate clinical picture, it is an indication for dual-chamber pacemaker implantation for first degree AV block without bradycardia or pauses.

Echocardiographic and Electrocardiographic Abnormalities Among Elderly Adults With Cardiovascular Disease in Rural South Africa.

Sub-Saharan Africa is undergoing an epidemiological transition fueled by the interaction between infectious and cardiovascular diseases. Our cross-sectional study aimed to characterize the spectrum of abnormalities suggesting end-organ damage on ECG and transthoracic echocardiograms (TTE) among older adults with cardiovascular diseases in rural South Africa. The prevalence of ECG and TTE abnormalities was estimated; χ2 analyses and multivariable logistic regressions were performed to test their association with sex, hypertension, and other selected comorbidities. Overall, 729 ECGs and 155 TTEs were completed, with 74 participants completing both. ECG evaluation showed high rates of left ventricular hypertrophy (LVH, 36.5%) and T wave abnormalities (13.6%). TTE evaluation showed high rates of concentric LVH (31.6%), with moderate-severe (56.8%) diastolic dysfunction. Participants with hypertension showed more cardiac remodeling on ECG by LVH (45.4% versus 22.1%, P<0.01), and TTE by concentric LVH (42.5% versus 8.2%, P<0.01) and increased left ventricular mass (58.5% versus 20.4%, P<0.0001). In multivariable logistic regression, systolic blood pressure remained significantly associated with LVH on ECG (adjusted odds ratio, 1.03 per mm Hg [95% CI, 1.03-1.04], P<0.0001) and increased left ventricular mass on TTE (adjusted odds ratio, 1.04 per mm Hg [95% CI, 1.01-1.06], P=0.001). Male participants (n=326, 40.2%) were more likely than females (n=484, 59.8%) to show ECG abnormalities like LVH (45% versus 30.8%, P<0.01), whereas females were more likely to show TTE abnormalities like concentric LVH (40.8% versus 13.5%, P<0.01) and increased left ventricular mass (58.4% versus 23.1%, P<0.0001). Similar results were confirmed in multivariable models. Our findings suggest that cardiovascular diseases are widespread in rural South Africa, with a larger burden of hypertensive heart disease than previously appreciated, and define the severity of end-organ damage that is already underway. Local health systems must adapt to face the growing burden of hypertension, as suboptimal rates of hypertension diagnosis and treatment may dramatically increase the heart failure burden.