Signs Of Left Ventricular Hypertrophy Research Articles

A Case of Symptomatic Hypertrophic Cardiomyopathy with Severe Dynamic Gradient

Hypertrophic cardiomyopathy is a disease of the myocardium characterized by the thickening of the heart walls. It is a genetic disorder transmitted by first-degree relatives, caused by mutations in genes that code for sarcomere protein. A 77-year-old woman presented to the emergency department and complained of continuous vertigos and presyncope with subsequent fall to the floor with a concussive traumatic brain injury. The ECG observed signs of left ventricular hypertrophy. Blood exams highlighted a slight increase of troponin T (25 ng/L). The ultrosonography instead demonstrated a pronounced left ventricular hypertrophy with a 240 mmHg dynamic gradient, a moderate mitral regurgitation secondary to SAM. Lastly, ECG Holter excluded significant arrhythmias (1 couple of ventricular contractions). In the ward, the echocardiographic pattern was repeated and confirmed the clinical picture of a pronounced ventricular hypertrophy at the expense of the IVS (VTD 45 ml), a diastolic dysfunction Grade I with anterior systolic movement of the mitral flap valves with a dynamic obstruction to the left ventricular outflow (DP max 260 mmHg). Moreover, a moderatesevere mitral insufficiency was reported. Vital signs were stable. The antihypertensive therapy was enhanced with added ACE inhibitors, loop diuretics, beta blockers and the disopyramide administration started. The patient was discharged from the hospital and was scheduled a cardiologic echocardiographic follow up in order to evaluate the effectiveness of the therapy. This study has demonstrated the association between the clinical symptom, the clinical objectivity and the echocardiographic anomalies typical of the obstructive hypertrophic cardiomyopathy. Severe blood pressure values of dynamic obstruction to the left ventricular outflow have been recorded and which are not currently known by the scientific literature. Our purpose will be to evaluate the clinical and echocardiographic follow up and the potential response to the pharmacological therapy prescribed.

Reactive Oxygen Species Produced by NADPH Oxidase Contribute to Cardiac Pathology in a Mouse Model of Sickle Cell Disease

Cardiopulmonary complications are an important contributor to morbidity and mortality in patients with sickle cell anemia (SCA). We have recently discovered that patients with SCA develop cardiomyopathy with restrictive pattern, characterized by diastolic dysfunction with progressive left atrial dilation, superimposed on the anemia-associated hyperdynamic physiology causing hypertrophied, dilated ventricles (Niss et al, JACC: Cardiovascular Imaging, 2016). Using a longitudinal systematic analysis of mouse models of SCA versus mice with iron-deficiency anemia, we found that this unique cardiomyopathy is indeed not due to chronic anemia and is associated with upregulation of genes related to oxidative stress pathways (Bakeer et al, PNAS, in press). These findings along with the known fact of increased inflammation and oxidative stress in SCA led us to postulate that NADPH oxidase (Nox)-mediated reactive oxygen species (ROS) may be an important pathogenic mechanism underlying cardiomyopathy in SCA and consequently mice lacking Nox-mediated ROS might be relatively protected from cardiac dysfunction.To investigate the role of NADPH oxidase in SCA cardiovascular pathophysiology, we bred the knock-in humanized SCA murine model Hbbtm2(HBG1,HBB*)Tow (where mouse α- and β-globin genes have been replaced by the human α- and βS globin genes; commonly known as UAB mice and herein called SS mice) with mice knocked out for the p22phox subunit of NADPH oxidase (a common subunit for all mouse Nox isoforms). We evaluated the phenotype of SS;p22phox-/- mice in blood and determined their cardiac function as compared to SS (p22phox+/+) littermate control mice. Hemolysis and ensuing reticulocytosis did not appear significantly improved in the SS;p22phox-/- mice; red blood cell (RBC) ROS was also stable likely due to the major contribution of mitochondrial ROS in the reticulocytes. Baseline ROS levels in the neutrophils of SS;p22phox-/-mice were similar to the levels in SS mice, but inducible ROS was almost eliminated as expected with deficiency of the p22phox subunit and inactivation of all NADPH oxidase isoforms.Starting at 8 weeks of age, cardiac structure and function were assessed on age-matched SS and SS;p22phox-/- mice by serial echocardiography. We studied 3 timepoints: 8-15 weeks of age, 16-24 weeks, and 25-34 weeks. SS mice developed progressively increased left atrial dimension (LAd) starting at 16 weeks of age while SS;p22phox-/- mice had stable LAd, with values similar to WT (Figure 1A). This difference became more pronounced with aging (P=0.02 at 25-34 weeks). Isovolumic relaxation time (IVRT), the time interval between closure of the aortic valve and opening of the mitral valve, was prolonged in the SS mice older than 16 weeks of age, consistent with diastolic dysfunction. In contrast, SS;p22phox-/- mice had no change in IVRT (Figure 1B). Also consistent with diastolic dysfunction, the ratio of transmitral E and e-(MV IVS E/e-) was increased in the SS group vs SS;p22phox-/-. Finally, the SS mice showed elevated left ventricular (LV) mass and decreased LV shortening fraction by 22-34 weeks whereas these parameters were preserved in the SS;p22phox-/-mice.Histopathology studies were performed to evaluate changes in the cardiac tissue. In the SS mice, H&E, picrosirius red and Masson trichrome staining showed not only significant LV hypertrophy and dilation but also significant interstitial fibrosis. Immunostaining for the extracellular matrix proteins collagen and fibronectin, showed extensive deposition of these proteins in the SS mouse heart. In contrast, SS; p22phox-/-mouse hearts were relatively spared.In conclusion, our data show that SS;p22phox-/-mice demonstrate better preserved diastolic and systolic heart function compared to SS mice, and decreased heart tissue damage. These findings suggest that therapeutic manuevers aimed at decreasing oxidative stress in SCA may be an effective strategy to counter SCA cardiomyopathy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Estrogen receptor antagonism exacerbates cardiac structural and functional remodeling in female rats.

We assessed the estrogen receptor (ER) dependence of female-specific cardioprotection using a rat model of chronic volume-overload stress. ER antagonism worsened ventricular wall stress, ventricular dilation, and cardiac dysfunction induced by volume overload. Further, blocking ERs resulted in cardiac remodeling and functional changes similar to that previously found in ovariectomized rats.

Impact of Afterload Increase on Left Ventricular Myocardial Deformation Indices

Left ventricular (LV) afterload could be associated with reduced myocardial contractility. The aim of this study was to evaluate the relative impact of increased afterload on LV myocardial deformation indices in chronic aortic constriction, with regard to hypertrophy, myocardial fibrosis, and mitochondrial function, and to differentiate acute versus chronic afterload effect. Young pigs underwent aortic banding (n=11) or sham (n=7) operations. Nineteen weeks later, LV morphology and systolic function, including myocardial deformation, were assessed by echocardiography before and after banding release or acute aortic constriction (in the sham group). After the animals were euthanized, mitochondrial function and LV interstitial fibrosis were assessed. The chronic banding group (n=8) presented with significant LV hypertrophy compared with the sham group (n=7), and longitudinal strain (LS) was significantly altered (16.9±0.7% vs 20.3±0.7%, P=.001) while circumferential, radial strain, and ejection fraction were not. LS abnormalities were situated mostly on the basal and mid segments and on the septal wall. There was also significantly more myocardial fibrosis in the chronic banding group compared with the sham group, while mitochondrial function was preserved. The relative contributions of hypertrophic and fibrotic remodeling and of afterload to alter global LS were 62%, and 38%, respectively. Acute aortic banding also significantly altered LS. The ratio of LS to septal wall thickness enabled differentiation between chronic and acute afterload increase (1.9±0.2 in the chronic group vs 2.9±0.3 in the acute group, P=.001). LS is susceptible to both hypertrophic and fibrotic remodeling and afterload increase, particularly on the basal and mid LV segments of the septum. The ratio of LS to septal wall thickness enables differentiation of acute from chronic afterload LS alteration.

Factors associated with diagnostic discrepancy for left ventricular hypertrophy between electrocardiography and echocardiography

Objective: To investigate the influence of cardiovascular risk factors, including fasting plasma glucose (FPG), on the association between electrocardiographic (ECG) and echocardiographic left ventricular hypertrophy (LVH) in an elderly population.Methods: We tested cross-sectional associations between electrocardiographic and echocardiographic LVH, defining LVH according to the Sokolow-Lyon voltage combination, Cornell voltage-duration product, or left ventricular mass index (LVMI). Differences between standardized LVMI and Sokolow-Lyon voltage combination or Cornell voltage-duration product (absolute value/cut-off value for LVH) were used as outcome variables in order to identify explanatory variables associated with diagnostic discrepancies between ECG and echocardiography.Results: Of the 1382 subjects included, 77% did not display any signs of LVH, 6% had LVH defined by ECG only, 13% had LVH defined by echocardiography only, and 5% had LVH on both ECG and echocardiography. Older subjects and those with higher blood pressure and RWT were more likely to have a relatively greater LVMI on echocardiography than that predicted on ECG (odds ratio: 1.65 per 10 years (95% confidence interval (CI): 1.27-2.15), p = .0002, odds ratio: 1.17 per 10 mmHg (95% CI: 1.09-1.25), p < .0001, and odds ratio: 1.21 per 0.10 (95% CI: 1.02-1.42), p = .03). In addition, discrepancy was also seen in females and subjects receiving antihypertensive medication (odds ratio: 1.41 (95% CI: 1.04-1.89), p = .03 and odds ratio: 1.41 (95% CI: 1.06-1.87), p = .02), but FPG did not independently influence discrepancy between ECG and echocardiography.Conclusion: Age, blood pressure, female sex, greater RWT and use of antihypertensive medication were associated with a greater risk of non-consistency between LVH determined by ECG and echocardiography.

PS 11-44 FEATURES OF CENTRAL HEMODYNAMIC PARAMETERS IN HYPERTENSIVE PATIENTS AT HIGH RISK, HAVING THE SIGNS OF LEFT VENTRICULAR HYPERTROPHY

Objective: To conduct a comparative analysis of daily parameters of aortic pressure and stiffness in patients with metabolic syndrome (MS) and arterial hypertension of 1–2 degrees (AH) with signs of left ventricular hypertrophy (LVH) and without. Design and Method: 122 subjects with three or more criteria for MS. The inclusion criterion was the presence of arterial hypertension of 1–2 degrees. All patients underwent the echocardiography (MyLab 90, Esaote, Italy), based on the results of which the patients were divided into 2 groups. The group1 consisted of 53 subjects with signs of LVH (LVMI values for men ≥ 125 g/m2 for women ≥ 110 g/m2). Group 2 included 69 patients with MS and normal values of LVMMI. Patients were matched for age, height, systolic and diastolic BP. Structural and functional properties of large arteries were analyzed according to ambulatory BP monitoring BpLab (“Peter Telegin”, Russia) to estimate the average value of the central (aortic) pressure and vascular stiffness (SBPao, DBPao, MBPao, PPao, Aixao, RWTT). Results: At comparable office BP values compared groups differed significantly on the values of SBPao (in group 1 -133.7 ± 12.8 mmHg, in group 2–127.8 ± 8.7 mmHg, p < 0.01), MBPao (in patients with LVH–111.0 ± 11.5 mmHg, in patients with normal values LVMMI–105.4 ± 8.5 mmHg, p < 0.01) and PPao (group 1–44.7 ± 9.7 mmHg, in group 2–40.5 ± 5.5 mmHg, p = 0.01) with comparable values of DBPao (89.4 ± 9.3 and 87.5 ± 8.3 mmHg, respectively; p = 0.24). No significant differences in the average daily level of Aixao have been identified: patients with LVH–24.2 ± 12.5%, in the comparison group–21.4 ± 13.2% (NS). Indicator RWTT in group 1 was 130.9 ± 9.2 ms, in group 2–136.1 ± 9.6 ms (p < 0.01). Conclusions: In patients with metabolic syndrome the signs of left ventricle hypertrophy were accompanied by a deterioration of most daily parameters of central pressure and stiffness.

Adrenal Gland Under Pressure

A 74-year-old man was admitted for sudden onset of severe pain in the left thoraco-abdominal flank. He had no palpitations and no headache. Clinically, the patient presented diaphoresis and his systolic blood pressure was measured at 240 mmHg. He had a history of hypertension treated by metoprolol, hydrochlorothiazide, felodipin and quinapril. ECG showed only signs of left ventricular hypertrophy. Biology was normal except a slight renal impairment. Thoraco-abdominal computed tomography performed to exclude an aortic dissection revealed a huge left adrenal mass (80 mm) with a left perirenal hematoma. Patient was admitted in intensive care unit to control blood pressure. At that time, pheochromocytoma was clinically suspected. Repeated 24-hour urine fractionated metanephrines and catecholamines measurements showed elevation of normetanephrine and noradrenalin levels at 3.2- and 1.6-fold the upper limit of the normal range respectively (in 3 independent urine collections). Despite no clear cut-offs for urinary (nor) metanephrines values, we considered these increased levels as compatible with the diagnosis of pheochromocytoma. 18F-FDG PET/CT imaging showed an FDG-avid adrenal lesion without pathological uptake elsewhere. A laparoscopic left adrenalectomy was performed and pathological examination concluded to an infiltration of the adrenal gland by a clear-cell renal cell carcinoma. The present case focuses on the atypical presentation of a renal cell carcinoma. The adrenergic symptoms combined to the increased urinary normetanephrine levels suggested the diagnosis of pheochromocytoma but were probably related to catecholamines release caused by the hemorrhage of the renal cell carcinoma within the adrenal medulla.

“Study of Cardiovascular Manifestations in Ankylosing Spondylitis”

“Study of Cardiovascular Manifestations in Ankylosing Spondylitis”

Left ventricular systolic synchrony of patients with hypertensive heart failure but preserved ejection fraction and its impact on left ventricular function

Objective To investigate the systolic synchrony of the left ventricle in patients with left ventricular hypertrophy (LVH) or with heart failure but preserved ejection fraction (HF-PEF), and to evaluate the impact of systolic dyssynchrony on left ventricular function. Methods During June 2011 to May 2014, a total of 352 patients(160 males, 192 females, average age: (67.6±7.8)years) with essential hypertension (EH) were enrolled in this retrospective study. Ultrasonic and G-MPI were performed for assessment of left ventricular remodeling and systolic synchrony and the results were statistically analyzed by one-way analysis of variance and χ2 test. Relationship between BNP and synchronic parameters as well as other clinical factors were analyzed by partial correlation analysis. Results The EH patients were divided into hypertension group (n=182), LVH group (n=74) and HF-PEF group (n=96). In comparison to hypertension group, significant LVH developed in LVH and HF-PEF groups although the LVEF was still preserved. The LVMI of the 3 groups were (94.4±10.1), (121.1±9.8) and (123.2±10.9) g/m2, respectively(F=8.66, P 0.05). Diastolic dysfunction was identified in LVH and HF-PEF groups with significantly reduced E/A ratio (1.19±0.23, 0.80±0.28, 0.67±0.17; F=13.46, P<0.05). Remarkable left ventricular systolic dyssynchrony with phase histogram bandwidth (PHB) of (88.4±8.6)° and phase standard deviation (PSD) of (23.6±1.9)° and increased BNP of (228.4±69.7) ng/L were revealed in HF-PEF group. The BNP in HF-PEF group was significantly higher than that in LVH group((92.5±13.6) ng/L; q=8.63, P<0.05). Positive correlation was found between BNP level and PHB, PSD, LVMI, respectively (r=0.277-0.331, all P<0.05). Conclusion Left ventricular systolic dyssynchrony is concomitant with HF-PEF patients induced by EH, and this dyssynchrony might be one of the factors leading to diastolic dysfunction. Key words: Heart failure; Hypertension; Stroke volume; Tomography, emission-computed, single-photon; Ultrasonography; MIBI

Soluble guanylate cyclase stimulator riociguat and phosphodiesterase 5 inhibitor sildenafil ameliorate pulmonary hypertension due to left heart disease in mice

BackgroundPresence of pulmonary hypertension (PH) and right ventricular dysfunction worsens prognosis in patients with chronic heart failure (CHF). Preclinical and clinical studies suggest a role for the impaired nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway in both PH and CHF. Hence, we examined the effects of the NO–sGC–cGMP pathway modulation by the PDE5 inhibitor sildenafil or sGC stimulator riociguat on pulmonary hemodynamics and heart function in a murine model of secondary PH induced by transverse aortic constriction. MethodsC57Bl/6N mice were subjected to transverse aortic constriction (TAC) for 6weeks to induce left heart failure and secondary PH and were subsequently treated with either sildenafil (100mg/kg/day) or riociguat (10mg/kg/day) or placebo for 2weeks. ResultsSix weeks after surgery, TAC induced significant left ventricular hypertrophy and dysfunction associated with development of PH. Treatment with riociguat and sildenafil neither reduced left ventricular hypertrophy nor improved its function. However, both sildenafil and riociguat ameliorated PH, reduced pulmonary vascular remodeling and improved right ventricular function. ConclusionsThus, modulation of the NO–sGC–cGMP pathway by the PDE5 inhibitor sildenafil or sGC stimulator riociguat exerts direct beneficial effects on pulmonary hemodynamics and right ventricular function in the experimental model of secondary PH due to left heart disease and these drugs may offer a new therapeutic option for therapy of this condition.

Distinct Endothelial Cell Responses in the Heart and Kidney Microvasculature Characterize the Progression of Heart Failure With Preserved Ejection Fraction in the Obese ZSF1 Rat With Cardiorenal Metabolic Syndrome.

The combination of cardiac and renal disease driven by metabolic risk factors, referred to as cardiorenal metabolic syndrome (CRMS), is increasingly recognized as a critical pathological entity. The contribution of (micro)vascular injury to CRMS is considered to be substantial. However, mechanistic studies are hampered by lack of in vivo models that mimic the natural onset of the disease. Here, we evaluated the coronary and renal microvasculature during CRMS development in obese diabetic Zucker fatty/Spontaneously hypertensive heart failure F1 hybrid (ZSF1) rats. Echocardiographic, urine, and blood evaluations were conducted in 3 groups (Wistar-Kyoto, lean ZSF1, and obese ZSF1) at 20 and 25 weeks of age. Immunohistological evaluation of renal and cardiac tissues was conducted at both time points. At 20 and 25 weeks, obese ZSF1 rats showed higher body weight, significant left ventricular hypertrophy, and impaired diastolic function compared with all other groups. Indices of systolic function did not differ between groups. Obese ZSF1 rats developed hyperproliferative vascular foci in the subendocardium, which lacked microvascular organization and were predilection sites of inflammation and fibrosis. In the kidney, obese ZSF1 animals showed regression of the peritubular and glomerular microvasculature, accompanied by tubulointerstitial damage, glomerulosclerosis, and proteinuria. The obese ZSF1 rat strain is a suitable in vivo model for CRMS, sharing characteristics with the human syndrome during the earliest onset of disease. In these rats, CRMS induces microvascular fibrotic responses in heart and kidneys, associated with functional impairment of both organs.

Pharmacologic Treatment with a Melanocortin Analogue Protects Against Pressure‐Overload Induced Cardiac Hypertrophy

PurposeHypertrophic growth of the heart is a consequence of heart ability to adapt to an increased afterload and wall stress. Although left ventricular hypertrophy (LVH) may resolute with adequate therapy, this process increases the amount of irreversible cardiac fibrosis.These morphological and functional changes in the myocardium may manifests as arrhythmias and congestive heart failure (CHF).Melanocortins regulate important physiological functions such as energy balance and blood pressure, but their long‐term effects on cardiac remodeling remain unexplored.In the present study, we investigated whether melanocortins affect physiological or pathologic cardiac growth and function.MethodsFirst, we studied the effects of transgenic melanocortin overexpression (MSH‐OE) on physiological age‐related cardiac growth in mice. Second, we examined the effects of a stable melanocortin analogue (MT‐II) on pressure overload‐ induced cardiac hypertrophy. We subjected 8‐week‐old C57Bl/6N mice to pressure‐overload by transverse aortic constriction (TAC) and randomly assigned the mice to receive daily i.p. injections of either vehicle (physiological saline) or MT‐II (0.3 mg/kg) for 6 weeks starting 2 weeks after surgery.ResultsAt the age of 6 months, MSH‐OE mice (n=11) had lower heart weight and smaller myocytes with maintained cardiac function compared to their age‐matched wild‐type littermates (n=15) while no differences in heart weight were noted at the age of 3‐months, indicating that melanocortin overactivity restrains age‐related cardiac growth. Eight weeks of pressure‐overload induced significant left ventricular (LV) hypertrophy with decreased cardiac function in saline‐treated TAC mice (n=15) compared to sham‐operated control mice (n=9).This pathologic cardiac remodeling was attenuated in MT‐II‐treated TAC mice (n=9) (Figure 1. and 2.). Importantly, MT‐II‐treatment did not compromise cardiac function, but tended to maintain LV contractility of TAC mice. Using quantitative NMR scanning to analyze body composition, we demonstrate that MT‐II treatment also prevented the deterioration of body weight development associated with the hypertrophic disease state.MT‐II treatment attenuated also the expression of genes regulating cardiac remodeling related mRNAs such as NppA, NppB, MMP‐2 and Col1a2.ConclusionsAlthough the underlying mechanisms remain largely unclear, these results, for the first time, establish melanocortin signaling as an antihypertrophic regulator and suggest that melanocortin analogues may be potential therapeutic tools for the treatment of cardiac hypertrophy and heart failure.Support or Funding InformationAcademy of Finland, Finnish Cultural Foundation

Lysyl Oxidase Inhibition Alleviates Fibrosis and Dysfunction in Rodents with Established Cardiac Disease

Heart failure is the end result of many cardiovascular disorders, including myocardial infarction, hypertension, and diabetes. Regardless of etiology, a key mechanism of heart failure is adverse extracellular matrix (ECM) remodeling. Lysyl oxidase (LOX) is a collagen cross‐linking enzyme that is elevated in failing human hearts, and is associated with cardiac fibrosis. Our goal for this study was to determine if inhibition of LOX in rodents with established cardiac disease would provide protection against further adverse cardiac remodeling and dysfunction. The aortocaval fistula rat surgical model of volume overload (VO) was used. Eight weeks after surgery, both sham‐operated and VO rats were treated with a LOX inhibitor, beta‐aminopropionitrile (BAPN; 100 mg/kg/d). Treatment was administered for six weeks using an osmotic minipump inserted into the peritoneal cavity.Echocardiography was used to assess progressive alterations in cardiac remodeling and function. At 14 weeks, left ventricular (LV) catheterization was used to assess alterations in contractility, stiffness, and other indices of cardiac function. Using LV homogenates and fixed sections, interstitial myocardial collagen (immunohistochemistry), and protein expression of collagens I and III (Western Blot) were measured. Collagen cross‐linking was assessed using pyridinoline (Pyd) assay.VO induced significant LV hypertrophy (116% increase vs sham), diastolic LV wall stress (363% increase vs sham), fibrosis (172%, 77% and 22% increase in interstitial myocardial collagen, collagen I and collagen III, respectively, vs sham; p&lt;0.05), and cardiac dysfunction (17% decrease in ejection fraction vs sham). LOX inhibition partially attenuated VO‐induced increases in LV hypertrophy (23% decrease vs VO; p&lt;0.05). Inhibiting LOX also completely attenuated VO‐induced increases in interstitial myocardial collagen, and protein expression of collagens I and III (180%, 76% and 22% decrease, respectively, vs VO; p&lt;0.05). LOX inhibition significantly attenuated increases in cardiac wall stress (33.5% decrease vs VO) and conferred cardioprotective effects as indicated by improved fractional shortening (19% increase vs untreated VO; p&lt;0.05). LOX inhibition also significantly attenuated VO‐induced decreases in contractility, assessed using end systolic pressure‐volume catheterization and preload recruited stroke work (70% and 30% increase, respectively, vs VO; p&lt;0.05). Overall, our data demonstrate the cardioprotective effects of LOX inhibition on the volume overload stressed heart, and its potential to slow or even prevent the transition to heart failure.Support or Funding InformationSupported by the NIH/NCRR #P20RR016456 and the American Heart Association Greater Southeast Affiliate #11GRNT7700002 (jdg).

Spontaneous Hypertension in Nonhuman Primate African Green Monkeys Is Associated with Left Ventricular Hypertrophy Without Significant Cardiac or Aortic Fibrosis

The African Green Monkey (AGM; Chlorocebus aethiops sabeus) develops hypertension in approximately 35% of individuals. It is likely that this hypertension is associated with elevated sympathetic nerve activity since hypertensive (HT) AGMs have significantly elevated heart rates compared to normotensive (NT) animals. Thus, hypertension in the AGM may exhibit elevated total peripheral resistance and increased cardiac after load that would lead to elevated left ventricular end systolic pressure. We hypothesize that in AGMs, chronic spontaneous hypertension elicits significant left ventricular hypertrophy (LVH), and increased myocardial and/or aortic collagen deposition compared with NT AGMs. Sedated AGMs were characterized as either HT (SBP≥140mmHg) or NT (SBP&lt;120mmHg) using forearm plethysmography (ketamine HCl, 15 mg/kg i.m.). Cardiac and aortic tissues were obtained immediately following euthanasia (Na+ pentobarbital overdose; 150 mg/kg i.v.). Cardiac and aortic tissues were fixed with paraformaldehyde (5%) and stored in ethanol (70%) or rapidly frozen and stored at −20 °C in isopentane. Fixed ventricular and aortic cross sections were cut (5 μm), mounted and stained with hematoxylin and eosin. Randomly selected colony HT AGMs had increased left ventricular myocardial cell area compared with NT animals (1658± 515 μm2, n=6, HT vs. 791± 210 μm2, n=7, NT; p&lt;0.01). Ventricular and aortic fibrosis was assessed using picosirius red stain which selectively identifies collagen deposition in tissue. Average area of collagen was greater in HT compared to NT AGMs (55.27 ± 2.33%, n=9 NT vs. 66.12 ± 4.22%, n=6 HT; p&lt;0.05). No difference was measured in average area of collagen per left ventricular myocardial tissue area between HT and NT AGMs (12.22 ± 0.80%, n=10 NT vs. 14.17 ± 3.29%, n=9 HT; p=0.84). Next, total tissue collagen was measured by quantifying tissue hydroxyproline from frozen aorta and left ventricular myocardium. Collagen content between HT and NT AGMs were not different in aorta (745.64 ± 44.49 μg/ml, n=11 HT vs. 668.39 ± 31.06 μg/ml, n=11 NT, p=0.17) or in left ventricular myocardium (194.02 ± 8.61 μg/ml, n=11 HT vs. 201.70 ± 18.89 μg/ml, n=10 NT, p=0.71). These results demonstrate that chronic elevation of blood pressure in AGM is associated with LVH. Despite this LVH in hypertensive AGM, collagen biosynthesis and deposition within aorta and left ventricular myocardium is similar to NT control animals. We conclude that AGMs with chronic elevation of arterial pressure develop LVH likely from increased after load arising from increased total peripheral resistance. This LVH however, must develop in response to factors other than increased deposition of intercellular collagen. Ongoing experiments in HT AGMs will assess the deposition of other intercellular connective proteins in both left ventricle and aorta as well as the presence of pro‐inflammatory cytokines known to contribute to LVH in other experimental models of hypertension.Support or Funding InformationSupported by American Physiological Society, National Science Foundation Integrative Organismal Systems Award No. IOS‐ 1238831, and Biomedical Science Research Group, L.L.C.

A stumbling block or a stepping stone?

Question A 60-year-old man, known with Fabry disease, secondary left ventricular hypertrophy, and moderate aortic valve stenosis had a check-up in the outpatient clinic. An electrocardiogram (ECG) at rest (Fig. 1) showed sinus rhythm, a short PR interval, QRS interval of 120 ms with a sharp initial part suggestive of pre-excitation, as well as other unchanged abnormalities, including signs of left ventricular hypertrophy. In order to examine this possible pre-excitation suggestive of a right-sided, septal bypass an exercise test was performed. Unfortunately, the test was stopped after only 2 min due to exhaustion with a maximal heart rate of only 83/minute, without changes in QRS morphology. Because of a negative history of collapse or palpitations no further diagnostic tests were performed. Four months later, he was admitted because of a collapse. The ECG at presentation is shown in Fig. 2. Fig. 1 ECG at rest Fig. 2 ECG in the emergency room What is your diagnosis, and what does it tell you about the possible pre-excitation? Answer You will find the answer elsewhere in this issue.

Limitations of N-Terminal Pro-B-Type Natriuretic Peptide in the Diagnosis of Heart Disease among Cancer Patients Who Present with Cardiac or Pulmonary Symptoms

Objectives: Recognizing heart disease is relevant to oncologists because cancer patients are at an increased risk of cardiac mortality due to shared risk factors and the adverse effects of cancer therapy. This study assessed the extent to which the measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) aids in the diagnosis of heart disease in addition to a history of coronary artery disease and the presence of atrial fibrillation (composite test). The NT- proBNP cutoff value was 100 pg/ml. Methods: A series of 583 consecutive cancer patients (68.4 ± 11.0 years) who were referred because of cardiac or pulmonary symptoms prospectively underwent a diagnostic work-up. Heart disease was diagnosed if at least one of the following conditions was present: (a) history of coronary artery disease, (b) atrial fibrillation, (c) impaired left ventricular systolic function, (d) significant valvular disease, (e) pulmonary hypertension, or (f) left ventricular hypertrophy. Results: Except for (a), all 6 conditions were associated with NT-proBNP >100 pg/ml. The sensitivity/specificity values of the composite test were 0.92/0.50 for any heart disease. Several extracardiac covariates were associated with NT-proBNP >100 pg/ml, which contributed to the low test specificity. Conclusions: The low specificity of NT-proBNP limits its value for the diagnosis of heart disease in cancer patients.

A case of apical hypertrophic cardiomyopathy presenting as acute coronary syndrome

Fig. 1. Normal left ventricular function and massive apical hypertrophy in 30° RAO. A 37-year old male patient was admitted to a hospital because of chest pain. His ECG revealed sinus rhythmand signs of left ventricular hypertrophy, but without giant negative T waves. At echocardiography left ventricular function was reduced at the apex suggesting positive left ventricular hypertrophy. Coronary arteries were normal, but left ventricular angiography revealed massive apical hypertrophy (Fig. 1). The diagnosis of apical form of hypertrophic cardiomyopathy could be obtained. Apical hypertrophic cardiomyopathy was first described in Japan, mostly with ECG features of giant negative T-waves [1]. In the following years more and more cases were described in other countries without giant negative T-waves. Complaints are: chest pain resembling acute coronary syndrome, exercise-induced dyspnea and sudden cardiac death due to ventricular fibrillation. In general, these are typical symptoms in hypertrophic cardiomyopathy, irrespective of the type of asymmetric hypertrophy: non-obstructive, obstructive or apical forms of hypertrophic cardiomyopathy. In our patient arrhythmias could be ruled out by normal Holtermonitoring and missing syncopes. A yearly follow-up is planned. Themedicationwith a beta blocking agent is reasonable, specially to prevent ventricular arrhythmias. If apical aneurysms can be obtained, the risk of ventricular arrhythmias is high and ICD implantation must be discussed in each single patient to prevent sudden cardiac death [2].

EKG und Sport

There was a longstanding controversy on the role of resting ECG in the preparticipation examination in athletes, as well as in children and adolescent, in leisure time or top athletes. Besides other arguments, this was due to the limited validity, to the false positive and false negative findings often followed by a thorough clinical examination. However, recent studies from different research groups yielded a significant improvement in establishing ECG criteria in athletes discriminating normal from abnormal or pathological findings in athletes.This in addition is supported and improved by a software-based ECG device considering the new Seattle criteria. These new criteria from the Seattle conference reliably discriminate normal from abnormal findings. Frequent ECG findings in athletes, especially in those engaged in endurance sports showed sinus bradycardia, AV-block and signs of left ventricular hypertrophy. Abnormal findings are related to structural left ventricular alterations due to cardiomyopathy, mainly hypertrophic with or without outflow tract obstruction, arrhythmogenic right ventricular cardiomyopathy (ARVC) and dilated cardiomyopathy. ECG findings suggestive of electrical diseases are observed in chanelopathies, WPW-syndrom supraventricular arrhythmias or disturbancies of cardiac conduction. The main diseases are long or short QT-syndrom, Brugada-­Syndrom and catecholaminergic polymorphic ventricular tachycardia. Recently, atrial fibrillation, mostly paroxysmal, is also more frequently observed especially in middle age endurance athletes. Interpretation of ECG in young and older athletes deserves in depth knowledge in cardiology and sports medicine as well. ECG interpretation can only be done considering history, clinical examination and ethnicity. Profound and longtime knowledge in athlete’s ECG interpretation is required to protect athletes and to prevent cardiac emergencies.

A Woman With Treatment-Resistant Hypertension.

Although this is not a particularly unusual or rare case of hypertension, it highlights the challenges we have as clinicians in managing such patients. The patient, a 60 year-old woman, was referred to the tertiary blood pressure clinic at Glasgow’s Western Infirmary 5 years ago by a consultant cardiologist for management of resistant hypertension. This lady has a vasculopathy with ongoing intermittent claudication and had previous bilateral superficial femoral artery occlusions on a background of hypercholesterolemia and a significant smoking history. The patient has problematic underlying ischemic heart disease, having had angina since 2001, numerous percutaneous interventions, and a 2-vessel coronary artery bypass graft. Despite this, she had a non–ST-segment–elevation myocardial infarction (MI) 2 years before presentation. Blood pressure at first visit to the clinic was 182/106 mm Hg despite numerous antihypertensive medications, including an angiotensin-converting enzyme inhibitor, calcium channel blocker, 2 different diuretics, α-blocker, and β-blocker in addition to her antianginal and secondary preventative medications (Table). Review of case notes and previous clinic documentation revealed that clinic blood pressure was elevated for at least 10 years with systolic readings ranging from 150 to 200 and diastolic between 90 and 100 mm Hg. View this table: Table. Total Daily Dose of Antihypertensive Medications: An Overview of Antihypertensive Medication at the Time of Referral to the Clinic (2010), Before RDN (2012) and Immediately After RDN (2012), and in 2015 The patient was admitted to the investigation ward for a week of workup. During this time, routine biochemistry showed normal renal function and electrolytes. Urine albumin/creatinine ratio was within the microalbuminuric range at 4.2 mg/mmol. Cardiac and mediastinal contours seemed normal on chest x-ray, and neither ECG nor echocardiogram showed significant left ventricular hypertrophy (LVH). No biochemical evidence to suggest pheochromocytoma or primary aldosteronism was found. Renal ultrasound exhibited 2 normal sized nonobstructed kidneys with no …

Abstract 19144: Echocardiographic Assessment of Structural and Hemodynamic Changes in Hypertensive Pregnancy

Introduction: Pregnancy induces dramatic cardiovascular changes to meet the metabolic needs for mother and fetus. Eccentric left ventricular hypertrophy (LVH) is known as the normal cardiac response to handle the increasing circulatory volume during pregnancy. Cardiac adaptation would be modified in pregnancy complicated by hypertension. Methods: Data from 193 consecutive pregnant women were analyzed. Clinical and echocardiographic data were compared in normotensive and hypertensive women. Results: Left ventricular mass index was significantly higher in hypertensive women than normotensive ones (87±17 vs 78±16, p&lt;0.001, Fig.1A). Diastolic function measured by the ratio of early mitral blood to annular velocity (E/E’) was impaired in hypertensive women (11.0±3.0 vs 9.2±2.5, p&lt;0.001, Fig.1B). Such change was more prominent in women with gestational hypertension (GHW) than those with chronic hypertension (CHW). Obesity was independent factor associated with LVH in both normotensive and hypertensive women (Fig.1C). Overt eccentric LVH was more frequent than concentric remodeling/hypertrophy (25% vs 8.4%) in GHW, while the result was opposite in CHW (14% vs 23%, Fig.1D). Conclusion: Hypertensive pregnancy is associated with significant LVH and diastolic dysfunction. Obesity accentuates hypertension-related cardiac remodeling. While eccentric LVH is prominent in GHW, pre-existing chronic hypertension appears to induce concentric LV geometry.