Echocardiographic Left Ventricular Wall Research Articles

Meteorin-like plasma levels as a novel biomarker for heart failure

Abstract Introduction Meteorin-like (metrnl), a new adipokine with insulin-sensitizing and anti-inflammatory action, has recently drawn much attention due to its protective effects in the cardiovascular system. Metrnl promotes heart repair after insults like ischemia/reperfusion, cardiotoxicity, or diabetic cardiomyopathy in mice, and its circulating levels in patients have been associated with the presence and severity of coronary artery disease and heart failure, although in the latter with contradictory results. Purpose Our aim was to study the correlation between plasma metrnl levels and biochemical and echocardiographic parameters in patients hospitalized with de novo heart failure (HF) to determine whether this adipokine could be a useful biomarker/therapeutic target for HF. Methods Blood samples of 400 patients hospitalized with de novo HF were collected in a multicenter clinical study. Plasma levels of metrnl were measured by enzyme-linked immunosorbent assay. Results In de novo HF patients, metrnl plasma levels were positively correlated with age (r = 0.322, P < 0.0001), NT-proBNP (r = 0.293, P < 0.0001), troponin (r = 0.192, P < 0.001), creatinine (r = 0.353, P < 0.0001) and urea (r = 0.322, P < 0.0001), while negatively correlated with albumin (r = -0.308, P < 0.0001) and alanine aminotransferase (r = -0.183, P < 0.0001). Metrnl plasma levels were also positively correlated with echocardiographic data of cardiac morphology as intraventricular septum thickness (r = 0.197, P < 0.0001) and left ventricular posterior wall thickness (r = 0.150, P < 0.004). On the other hand, Cox regression analysis suggested that higher plasma metrnl was associated with increased cardiovascular mortality (HR, 1.004, P < 0.004)) and rate of readmission for HF (HR, 1.002, P < 0.008). Regarding the different types of HF, we found that metrnl plasma levels were lower in HF with reduced ejection fraction (HFrEF) in comparison those with preserved ejection fraction (HFpEF) [408.06 (354.05 - 537.71) pg/mL vs. 486.06 (391.94 – 607.80), median (interquartile range), respectively; P < 0.0001]. Conclusion Metrnl plasma levels were associated with markers of cardiac (troponin), renal (creatinine and urea) and hepatic (alanine aminotransferase and albumin) damage. The HF marker NT-proBNP and the echocardiographic parameters intraventricular septum thickness and left ventricular posterior wall thickness are also linked to metrnl plasma levels. Moreover, metrnl levels were found to be independent predictors of cardiovascular mortality and readmission for heart failure. And finally, metrnl plasma levels in patients hospitalized with de novo HF were increased in patients with HFpEF vs. HFrEF. Our results reinforce the relevance of the adipokine metrnl in the pathophysiology and diagnosis of HF, and supports its possible use in the future as biomarker/therapeutic target for HF.

Electrocardiogram evolution in Anderson-Fabry disease patients during follow-up

Abstract Background Anderson-Fabry disease (AFD) is a rare and progressive X-linked metabolic disorder caused by mutations in alfa galactosidase A gene, which leads to a pathologic, multiorgan, accumulation of ceramides with cytotoxic, proinflammatory and fibrotic effects. Cardiovascular involvement represents one of the main causes of death. Although ECG has proven to be useful for early AFD recognition, little evidence is available on the evolution of ECG alterations during follow-up. Purpose and Methods The aims of the study were to describe ECG changes during a long-term follow up, and to evaluate their association with the progression of cardiac involvement. The presence of interactions between ECG changes and specific AFD therapy (treatment status) were also evaluated. 219 AFD patients from a multicentre cohort underwent 12-lead ECG extensive analysis, transthoracic echocardiography, and complete clinical evaluation. Results After the exclusion of 3 patients with a permanent pacemaker, 5 with poor ECG quality, 2 with only one ECG, and 18 ≤18 years old, 181 AFD patients composed the final cohort (age 46 [IQR 35-58], 36% male, 67% classic phenotype). Treatment status (either enzyme replacement or chaperone molecules) was distributed as follows: chronic therapy for at least one year (24%), specific therapy started during the follow up (39%), no specific therapy (37%). During a median follow up of 62 months (IQR 33-83 months), several ECG parameters showed significant changes: atrial fibrillation detection (p<0.001), PQ interval (p=0.004), left atrial enlargement (p=0.001), a new right bundle branch block (RBBB, p<0.001), QRS interval (p<0.001) and QRS fragmentation (p=0.022), QTcB interval (p=0.001), and negative T waves development (p=0.001) mostly lateral and symmetric (p=0.016). Among these, PQ interval showed a significant interaction with treatment status being significantly altered only in patients in the chronic therapy and no specific therapy groups, being stable in patients who started the specific therapy during the follow up (p for interaction=0.048). In addition, PQ, QRS interval duration, a new RBBB, and a new pathologic QT interval were associated with the evolution of the echocardiographic maximal left ventricular (LV) wall thickness during the follow up on univariable analysis, with the QRS duration losing the statistical significance on multivariable analysis but still showing a trend (p=0.089) toward an association with an increased LV wall thickness. Conclusions In this multicentric cohort of AFD patients, different ECG parameters underwent significant changes during follow-up. Of these, PQ interval duration showed a significant interaction with the specific therapy status in that it did not increase in patients who started the therapy at the begin of the follow up. PQ interval, a new RBBB and pathologic QTc development were also significantly associated with the progression of LV hypertrophy on multivariable analysis.Table 1 and Table 2Figure 1

Transient receptor potential vanilloid 1-expressing cardiac afferent nerves may contribute to cardiac hypertrophy in accompany with an increased expression of brain-derived neurotrophic factor within nucleus tractus solitarius in a pressure overload model

ABSTRACT Introduction Increased sympathetic output contributes to cardiac hypertrophy. Sympathoexcitation is induced by activating the cardiac sympathetic afferent nerves through transient receptor potential vanilloid 1 (TRPV1) in cardiac afferent endings. Brainstem nucleus tractus solitarius (NTS) receives the sensory cardiac afferent inputs. Brain-derived neurotrophic factor (BDNF) is released within NTS from sensory neurons in an activity-dependent manner. Additionally, BDNF in NTS tonically regulates sympathetic activity. Therefore, we hypothesized that TRPV1-expressing cardiac afferent nerves contribute to cardiac hypertrophy in accompany with an increased BDNF expression in NTS. Methods and Results Abdominal aortic banding (AB) or sham operation was conducted in wild-type C57BL/6 J (WT-AB) and TRPV1 knockout mice (TRPV1 KO-AB). At 8 weeks post-operation, echocardiographic left ventricular wall thickness and heart weight/body weight ratio were significantly greater in WT-AB than WT-Sham mice, and these hypertrophic indexes were attenuated in TRPV1 KO-AB mice. Among the groups, left ventricular fractional shortening was not different. The protein levels of TRPV1 in heart and BDNF in NTS were significantly increased in WT-AB compared to WT-Sham mice, whereas BDNF expression in NTS was not increased by AB in TRPV1-KO mice. Chemical ablation of TRPV1-expressing cardiac afferents attenuated the AB-induced cardiac hypertrophy and increase in BDNF in NTS. Sympathetic activity analyzed using heart rate variability, and sympathoexcitatory responses to the stimulation of cardiac afferents were increased in WT-AB compared to WT-Sham mice. Conclusion TRPV1-expressing cardiac afferent nerves may contribute to pressure overload-induced cardiac hypertrophy in accompany with the increased BDNF within NTS.

Abstract 17200: Improving the Early Detection of Cardiac Amyloidosis: Experience From a Large Urban Academic Center

Introduction: Cardiac amyloidosis (CA) is associated with a poor prognosis and the condition is often overlooked or the diagnosis is delayed by an average of 2 years. With the availability of treatment, identifying patients early in the course of the disease could significantly improve outcomes associated with CA. We describe the characteristics of patients with suspected CA and factors associated with obtaining a 99m Technetium-pyrophosphate ( 99m Tc-PYP) scan. Methods: We systematically reviewed and abstracted data from electronic medical records of 199 patients at the Grady Memorial Hospital in Atlanta, Georgia, between January 2018 to October 2019. Eligible patients had an echocardiographic left ventricular posterior wall (LVPWd) or interventricular septal wall (IVSd) thickness in diastole ≥ 1.4 cm and no evidence of aortic stenosis. Descriptive analyses were performed using SAS 9.4. Results: Mean age of sample was 65 ± 13 years (96% blacks, 40% women). Over 72% had health insurance, 87% had an LV ejection fraction > 50%, 52% had a diagnosis of heart failure (HF), and 31% had associated peripheral neuropathy. Fifty-nine (30%) patients had a 99m Tc-PYP scan, 10 had a cardiac MRI and only 1 had an endomyocardial biopsy. Of the 4 patients with confirmed CA, mean age was 79 ± 5 years, mean IVSd was 1.7 ± 02 cm and mean LV mass index was 184 ± 33. All 4 patients were black males, had a 99m Tc-PYP scan and 3/4 had health insurance. Table 1 compares characteristics of patients who received a 99m Tc-PYP scan with those who did not. Overall, age, sex, health insurance status, presence of HF and LVH were not associated with the odds of obtaining a 99m Tc-PYP scan. Conclusion: These preliminary results appear to demonstrate variability in diagnostic testing for CA among patients with similar demographic and bioclinical profiles. Understanding the reasons for these differences may be key in improving early testing and diagnosis of CA among our patient population.

Abstract 15808: Relationship Between Myocardial Injury, Wall Motion Abnormalities and Mortality in Patients With Covid-19: The Circ-19 Registry

Introduction: Myocardial injury is commonly observed in patients (pts) with Coronarvirus disease 2019 (Covid-19) but its anatomical correlate has not been elucidated. We evaluated the association between presence of transthoracic echocardiographic (TTE) left ventricular (LV) regional wall motion abnormalities (RWMA), myocardial injury and outcomes in Covid-19 pts. Methods: We conducted a cohort study including 7 hospitals in New York City (US) and Milan (Italy) of hospitalized pts with confirmed Covid-19 who had a TTE during their index hospitalization. Myocardial injury was defined as any elevation in cardiac troponin (cTn) during the hospitalization. Using multivariable logistic regression, we analyzed the association between RWMA, myocardial injury and in-hospital death. Results: Among 305 total pts included in the study, 49 (16%) had RWMA and 44 (14%) had global LV systolic dysfunction. Among those with RWMA, 31/49 (63%) had LV ejection fraction <50%. Compared to pts without RWMA, pts with RWMA more commonly had chest pain at time of presentation (36% vs. 14%; p=0.001), ST segment changes on ECG (33% vs. 6%; p<0.0001) and myocardial injury (90% vs. 57%; p<0.001). After multivariable analysis, RWMA remained associated with myocardial injury (adjOR: 5.92; 95% CI: 2.17-16.17), but not death. Left heart catheterization (LHC) was performed in 9 of the 49 (18%) pts with RWMA, 8 of which had confirmed ACS and 7 underwent PCI. Myocardial injury was associated with higher risk of death regardless of the presence or absence of RWMA ( Figure 1 ). Conclusion: In Covid-19 pts, RWMA are associated with typical ACS presentation: chest pain, ST changes and cTn elevations. Accordingly, a large proportion of pts with RWMA who underwent LHC had confirmed ACS warranting PCI. Though myocardial injury was associated with increased risk of in-hospital death regardless of the presence of RWMA, LHC should be considered for pts with RWMA and myocardial injury to rule-out obstructive disease.

Plasma brain natriuretic peptide level on admission predicts long-term outcome in patients with non-traumatic subarachnoid hemorrhage

IntroductionNon-traumatic subarachnoid hemorrhage (SAH) is a type of stroke that still has a high mortality rate. Some patients with SAH have electrocardiography (ECG) abnormalities or asymptomatic left ventricular apical ballooning, and requires intervention by cardiologists. However, the impact of cardiac abnormalities after SAH onset remains unclear. We investigated whether ECG abnormalities, myocardial damage, sympathetic nervous activity or echocardiographic left ventricular wall motion abnormalities (WMA) could provide additional risk stratification in patients with SAH. MethodsWe studied 118 SAH patients (78 women, age 63 ± 15) without a history of heart disease. Neurological grade (Hunt and Kosnik Grade) and clinical factors were evaluated. A standard 12-lead ECG, echocardiography and blood samples were obtained within 48 h after SAH onset. ECG abnormalities were defined as abnormal Q wave, ST elevation, giant T-wave inversion or QT prolongation. ResultsTwenty of 118 patients (17%) died during the follow-up (35 ± 31 months). Death was significantly associated with higher age (p < 0.0001), neurological grade (p < 0.0001), elevated BNP level (p < 0.0001), increased plasma norepinephrine levels (p < 0.0001) and WMA (p = 0.0070), while ECG abnormalities were not significantly associated. Neurological grade (p < 0.0001), age (p = 0.0047) and BNP (p = 0.0014, hazard ratio 1.0255 for each 1 pg/mL increase in BNP, 95%CI 1.0088 to 1.0499) were independently associated with death. Patients with BNP ≥ 96.6 had a higher risk of death (log- rank p < 0.0001). ConclusionPlasma BNP might provide an additional risk stratification in patients with non-traumatic SAH that requires intervention by cardiologists for both its prevention management after onset.

Risk of cardiovascular involvement in pediatric patients with X-linked hypophosphatemia.

To find out if cardiovascular alterations are present in pediatric patients with X-linked hypophosphatemia (XLH). Multicentre prospective clinical study on pediatric patients included in the RenalTube database ( www.renaltube.com ) with genetically confirmed diagnosis of XLH by mutations in the PHEX gene. The study's protocol consisted of biochemical work-up, 24-h ambulatory blood pressure monitoring (ABPM), carotid ultrasonography, and echocardiogram. All patients were on chronic treatment with phosphate supplements and 1-hydroxy vitamin D metabolites. Twenty-four patients (17 females, from 1 to 17years of age) were studied. Serum concentrations (X ± SD) of phosphate and intact parathyroid hormone were 2.66 ± 0.60mg/dl and 58.3 ± 26.8pg/ml, respectively. Serum fibroblast growth factor 23 (FGF23) concentration was 278.18 ± 294.45pg/ml (normal < 60pg/ml). Abnormally high carotid intima media thickness was found in one patient, who was obese and hypertensive as revealed by ABPM, which disclosed arterial hypertension in two other patients. Z scores for echocardiographic interventricular septum end diastole and left ventricular posterior wall end diastole were + 0.77 ± 0.77 and + 0.94 ± 0.86, respectively. Left ventricular mass index (LVMI) was 44.93 ± 19.18g/m2.7, and four patients, in addition to the obese one, had values greater than 51g/m2.7, indicative of left ventricular hypertrophy. There was no correlation between these echocardiographic parameters and serum FGF23 concentrations. XLH pediatric patients receiving conventional treatment have echocardiographic measurements of ventricular mass within normal reference values, but above the mean, and 18% have LVMI suggestive of left ventricular hypertrophy without correlation with serum FGF23 concentrations. This might indicate an increased risk of cardiovascular involvement in XLH.

Symptomatic Exercise-Induced Left Ventricular Outflow Tract Obstruction without Left Ventricular Hypertrophy

Left ventricular (LV) outflow tract obstruction (LVOTO) is most commonly seen in patients with hypertrophic cardiomyopathy. Postexercise dynamic LVOTO (DLVOTO) has been infrequently identified in symptomatic patients without LV hypertrophy, and its pathophysiology is not well established. The aim of this study was to identify echocardiographic abnormalities that might explain the dynamic development of systolic anterior motion, mitral-septal contact, and LVOTO in these patients. Patients with DLVOTO and normal wall thickness were compared with 20 age-matched and gender-matched controls with normal stress echocardiographic findings. Two other groups were also compared: patients with DLVOTO and mild segmental hypertrophy (segmental wall thickness ≤15 mm) and patients with normal left ventricles but DLVOTO after dobutamine stress. Six symptomatic patients were identified (mean age, 48 ± 9 years; range, 37-60 years; five men) with normal wall thickness who developed DLVOTO after exercise during a 6-year period. Five had been hospitalized for cardiac symptoms. The mean postexercise LV outflow tract gradient caused by systolic anterior motion mitral-septal contact was 107 ± 55 mm Hg (range, 64-200 mm Hg). All patients had echocardiographic LV wall thicknesses in the normal range (≤12 mm). Structural abnormalities of the mitral valve were identified in all six patients. These were elongated posterior leaflets (2.0 vs 1.5 cm, P < .0005), elongated anterior leaflets (3.2 vs 2.6 cm, P= .015), increased protrusion height of the mitral valve beyond the mitral annular plane (2.6 vs 0.6 cm, P < .00001), and residual protruding portions of the mitral valve leaflets (0.85 vs 0.24 cm, P < .005). There was anterior positioning of the papillary muscles in the LV cavity, with a greater distance from the plane of the papillary muscles to the posterior wall (1.8 vs 1.3 cm, P= .03). In two patients, potentially provoking medications were stopped; two patients received β-blockers, with reductions of angina. Medium-term prognosis was good; no patient had died after 3.5 years. The mitral valve abnormalities in the 10 patients with DLVOTO and mild segmental hypertrophy were qualitatively and quantitatively very similar to those in patients with DLVOTO without hypertrophy. In contrast, the valves of patients with dobutamine stress DLVOTO were not elongated, but 50% had residual mitral leaflets that protruded past the coaptation point by ≥5 mm. DLVOTO after exercise can occur in the absence of LV hypertrophy and may be associated with high gradients and cardiac symptoms. Elongated, redundant mitral valve leaflets with anterior position of the papillary muscles appear to cause the postexercise obstruction.

Role for MicroRNA-21 in Atrial Profibrillatory Fibrotic Remodeling Associated With Experimental Postinfarction Heart Failure

Atrial tissue fibrosis is often an important component of the atrial fibrillation (AF) substrate. Small noncoding microRNAs are important mediators in many cardiac remodeling paradigms. MicroRNA-21 (miR-21) has been suggested to be important in ventricular fibrotic remodeling by downregulating Sprouty-1, a protein that suppresses fibroblast proliferation. The present study examined the potential role of miR-21 in the atrial AF substrate resulting from experimental heart failure after myocardial infarction (MI). Large MIs (based on echocardiographic left ventricular wall motion score index) were created by left anterior descending coronary artery ligation in rats. Changes induced by MI versus sham controls were first characterized with echocardiography, histology, biochemistry, and in vivo electrophysiology. Additional MI rats were then randomized to receive anti-miR-21 (KD21) or scrambled control sequence (Scr21) injections into the left atrial myocardium. Progressive left ventricular enlargement, hypocontractility, left atrial dilation, fibrosis, refractoriness prolongation, and AF promotion occurred in MI rats versus sham controls. Atrial tissues of MI rats showed upregulation of miR-21, along with dysregulation of the target genes Sprouty-1, collagen-1, and collagen-3. KD21 treatment reduced atrial miR-21 expression levels in MI rats to values in sham rats, decreased AF duration from 417 (69-1595; median [Q1-Q3]) seconds to 3 (2-16) seconds (8 weeks after MI; P<0.05), and reduced atrial fibrous tissue content from 14.4 ± 1.8% (mean ± SEM) to 4.9 ± 1.2% (8 weeks after MI; P<0.05) versus Scr21 controls. MI-induced heart failure leads to AF-promoting atrial remodeling in rats. Atrial miR-21 knockdown suppresses atrial fibrosis and AF promotion, implicating miR-21 as an important signaling molecule for the AF substrate and pointing to miR-21 as a potential target for molecular interventions designed to prevent AF.

The occurrence of cardiovascular disease during 5-year follow-up in patients with idiopathic atrial fibrillation

Idiopathic atrial fibrillation (AF) may be an expression of as yet undetected underlying heart disease. We found it useful for clinical practice to study the long-term development of cardiovascular disease (CVD) in patients diagnosed with idiopathic AF. Forty-one consecutive idiopathic AF patients (56 ± 10 years, 66% male) were compared with 45 healthy control patients in permanent sinus rhythm. Patients were free of hypertension, antihypertensive and antiarrhythmic drugs, diabetes, congestive heart failure, coronary artery or peripheral vascular disease, previous stroke, thyroid, pulmonary and renal disease, and structural abnormalities on echocardiography. Baseline characteristics and echocardiographic parameters were equal in AF cases and controls. During a mean follow-up of 66 ± 11 months, CVD occurred significantly more often in idiopathic AF patients compared with controls (49 vs. 20%, P= 0.006). Patients with idiopathic AF were significantly younger at the time of their first CV event compared with controls (59 ± 9 vs. 64 ± 5 years, P= 0.027), and had more severe disease. Multivariable Cox regression analysis revealed that age, a history of AF, and echocardiographic left ventricular wall width were significant predictors of CVD development. Patients originally diagnosed with idiopathic AF develop CVD more often, at younger age, and with a more severe disease profile compared with healthy sinus rhythm control patients. The detection and treatment of CVD in an early stage could improve the prognosis of these patients. At present it seems prudent to regularly check idiopathic AF patients for the insidious development of CVD.

Recovery from long lasting life-threatening ventricular arrhythmia associated with fulminant myocarditis

A 39-year-old woman was referred because of a chest discomfort following flu symptoms (high grade fever, headache and arthralgia) in January 2008. Her consciousness was drowsy and her blood pressure was 86/62. Electrocardiogram revealed accelerated idioventricular rhythm (P and QRS rates were 140/min and 86/min respectively) (Fig. 1A). Chest X-ray showedmild lung congestionwith slight cardiac enlargement. A laboratory examination showed the following data: white blood cell count 9600/μL, asparate aminotransferase 442 IU/L, alanine aminotransferase 130 IU/L, lactate dehydrogenase 846 IU/L, creatine phosphokinase (CPK) 7298 IU/L, Na 135 mEq/L, K 5.9 mEq/L, C-reactive protein 6.94 mg/dL. Echocardiographic left ventricular (LV) wall motion was extremely reduced (LV ejection fraction of 17%) without valvular disease. Emergent coronary angiogram revealed normal coronary arteries. Just after admission, the accelerated idioventricular rhythm changed into a faster ventricular tachycardia (VT, cycle length of 444 ms) abruptly, then she collapsed (Fig. 1B). Lidocaine hydrochloride, Magnesium sulfate, nifekalant hydrochloride and direct current cardioversions (16 attempts on the first day) could not terminate this VT. Because of cardiogenic shock, intensive therapy with mechanical cardiac support should be started; PCPS, IABP and mechanical ventilation were required. PCPS and IABP were set through right and left femoral approaches, respectively. PCPS equipment was set as follows: membrane oxygenator and pump

Electrocardiographic markers predict left ventricular wall motion improvement in patients with acute myocardial infarction receiving thrombolysis

In patients with ST-elevation myocardial infarction (STEMI) treated with fibrinolysis, prediction of early left ventricular wall motion changes is important for prognosis. In 106 patients with STEMI treated with thrombolysis, we analyzed the degrees of total and maximal ST-segment resolution at 3 hours and changes in sums of T-wave amplitudes in leads with ST elevation 3 and 48 hours after thrombolysis as the predictors of the echocardiographic left ventricular wall motion score index (WMSI) improvement. Wall motion score index improvement was best predicted by total ST-segment resolution of more than 44% in anterior infarctions (sensitivity, 81%; specificity, 62%) and more than 59% in nonanterior infarctions (sensitivity, 100%; specificity, 42%) and by difference in sums of T-wave amplitudes between electrocardiograms at 48 hours and baseline less than -28 mm (sensitivity, 68%; specificity, 76%). In STEMI, the total ST-segment resolution 3 hours and T-wave changes at 48 hours after thrombolysis are the reliable predictors of the left ventricular WMSI improvement.

Role of Cardiac Magnetic Resonance Imaging in the Detection of Cardiac Amyloidosis

Our aim was to evaluate the role and mechanism of late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) in identifying cardiac amyloidosis (CA) and to investigate associations between LGE and clinical, morphologic, functional, and biochemical features. CA can be challenging to diagnose by echocardiography. Recent studies have demonstrated an emerging role for LGE-CMR. LGE-CMR was performed in 120 patients with amyloidosis. Cardiac histology was available in 35 patients. The remaining 85 patients were divided into those with and without echocardiographic evidence of CA. Of the 35 patients with histologically verified CA, abnormal LGE was present in 34 (97%) patients and increased echocardiographic left ventricular wall thickness in 32 (91%) patients. Global transmural or subendocardial LGE (83%) was most common and was associated with greater interstitial amyloid deposition (p = 0.03). Suboptimal myocardial nulling (8%) and patchy focal LGE (6%) were also observed. LGE distribution matched the deposition pattern of interstitial amyloid. Among patients without cardiac histology, LGE was present in 86% of those with evidence of CA by echocardiography and in 47% of those without evidence of CA by echocardiography. In patients without echocardiographic evidence of CA, the presence of LGE was associated with worse clinical, electrocardiographic (ECG), and cardiac biomarker profiles. In all patients, LGE presence and pattern was associated with New York Heart Association functional class, ECG voltage, left ventricular mass index, right ventricular wall thickness, troponin-T, and B-type natriuretic peptide levels. LGE is common in CA and detects interstitial expansion from amyloid deposition. Global transmural or subendocardial LGE is most common, but suboptimal myocardial nulling and focal patchy LGE are also observed. LGE-CMR may detect early cardiac abnormalities in patients with amyloidosis with normal left ventricular thickness. The presence and pattern of LGE is strongly associated with clinical, morphologic, functional, and biochemical markers of prognosis.

Cardiomyocyte-restricted restoration of nitric oxide synthase 3 attenuates left ventricular remodeling after chronic pressure overload

Although nitric oxide synthase (NOS)3 is implicated as an important modulator of left ventricular (LV) remodeling, its role in the cardiac response to chronic pressure overload is controversial. We examined whether selective restoration of NOS3 to the hearts of NOS3-deficient mice would modulate the LV remodeling response to transverse aortic constriction (TAC). LV structure and function were compared at baseline and after TAC in NOS3-deficient (NOS3(-/-)) mice and NOS3(-/-) mice carrying a transgene directing NOS3 expression specifically in cardiomyocytes (NOS3(-/-TG) mice). At baseline, echocardiographic assessment of LV dimensions and function, invasive hemodynamic measurements, LV mass, and myocyte width did not differ between the two genotypes. Four weeks after TAC, echocardiographic and hemodynamic indexes of LV systolic function indicated that contractile performance was better preserved in NOS3(-/-TG) mice than in NOS3(-/-) mice. Echocardiographic LV wall thickness and cardiomyocyte width were greater in NOS3(-/-) mice than in NOS3(-/-TG) mice. TAC-induced cardiac fibrosis did not differ between these genotypes. TAC increased cardiac superoxide generation in NOS3(-/-TG) but not NOS3(-/-) mice. The ratio of NOS3 dimers to monomers did not differ before and after TAC in NOS3(-/-TG) mice. Restoration of NOS3 to the heart of NOS3-deficient mice attenuates LV hypertrophy and dysfunction after TAC, suggesting that NOS3 protects against the adverse LV remodeling induced by prolonged pressure overload.

The Reliability of Echocardiographic Left Ventricular Wall Motion Index to Identify High‐Risk Patients for Multicenter Studies

To study whether the use of echocardiographic left ventricular (LV) wall motion index (WMI) is a dependable parameter for identifying patients with LV dysfunction to be enrolled in multicenter trials. Videotaped echocardiographic examinations from 200 randomly selected patients that were screened for inclusion into the DIAMOND-CHF and DIAMOND-MI trials were reevaluated by an external expert echocardiographer. WMI was calculated using the 16-segment LV model. The external echocardiographer systematically found lower values of WMI than the core laboratory. The average difference in WMI was 0.18 (SD: 0.33) in the DIAMOND-CHF trial and 0.09 (SD: 0.33) in the DIAMOND-MI trial. The difference in WMI exceeded 0.33 in 34% of the patients in both trials. The cutoff value for inclusion into the DIAMOND trials was WMI < or = 1.2. There was an agreement on WMI dichotomized to below or above 1.2 in 82% of the patients in both trials (kappa coefficient 0.66 for the DIAMOND-CHF and 0.55 for the DIAMOND-MI). Despite substantial interlaboratory variation in WMI in individual patients and a systematic lower WMI score by the external echocardiographer there was an acceptable overall agreement for identifying patients with severe impairment of LV function. This not only underscores the value of LV-WMI as a useful tool for selecting high-risk patients to be included in multicenter studies but also serves to warn against the use of rigid cutoff values for WMI in the treatment of individual patients.

An Echocardiographic Left Ventricular Wall Area Index for Functional Detection of Myocardial Injury in Hemodynamically Unloaded Hearts

Functional assessment of the left ventricle is affected by loading conditions. Detection of rejection-mediated myocardial injury in a heterotopic heart transplant model is a challenge for the echocardiographer because the heart is in an unloaded state. We examined the relationship of a novel left ventricular (LV) wall area index (LVWAI) and serum cardiac troponin T (cTnT) levels. The LVWAI, based on prior methods of determining LV mass, was defined as the difference between epicardial and endocardial areas divided by the epicardial area. The biphasic morphometric response of LVWAI reflected changes in the cTnT levels and allowed echocardiographic detection of myocardial injury in hemodynamically unloaded hearts.

Effect of Losartan on Left Ventricular Diastolic Function in Patients With Nonobstructive Hypertrophic Cardiomyopathy

In hypertrophic cardiomyopathy (HC), diastolic dysfunction of the left ventricle is a prominent feature caused by myocardial hypertrophy and fibrosis. Angiotensin II has trophic and profibrotic effects on the heart, and the blockade of angiotensin II receptors reverses hypertrophy and fibrosis in human cardiac diseases and in animal HC. This study investigated the short-term (6 months) effects of losartan 100 mg/day in 20 patients with nonobstructive HC, with an emphasis on left ventricular (LV) diastolic dysfunction, compared with 10 patients with HC who were not treated. At the final evaluation, significant changes were observed in the losartan group: a left atrial diameter decrease (p<0.0001), a tissue Doppler early (Ea) mitral annulus diastolic velocity increase (p=0.003) and an E/Ea ratio decrease (p=0.0002), and a significant decrease in plasma levels of the aminoterminal fragment of pro-brain natriuretic peptide (NT-pro-BNP) from a median of 860 to 606 pg/ml (p=0.001). A significant correlation was found between percentage changes in NT-pro-BNP and the E/Ea ratio from baseline to 6 months (r=0.61, p=0.002). In the 2 groups, echocardiographic LV wall and cavity measures did not change. In conclusion, in selected patients with nonobstructive HC, losartan during a 6-month period improved LV diastolic function.

Relation of echocardiographic left ventricular mass, geometry and wall stress, and left atrial dimension to coronary calcium in young adults (the CARDIA study)

We examined the relation of measures of echocardiographic left ventricular mass and geometry with coronary artery calcium (CAC) in 2,724 young adults. After adjustment for other coronary risk factors, left atrial dimension remained associated with the presence of CAC, and among subjects positive for CAC, left ventricular mass, end-systolic stress, and septal and posterior wall thicknesses in diastole remained associated with an increased extent of CAC.

Aortic regurgitation in the heterotopic rat heart transplant: effect on ventricular remodeling and diastolic function

Objectives Use of the heterotopic rat cardiac isograft model is limited by ventricular atrophy attributable to the left ventricle’s non-working state. Previous studies indicate that increased left ventricular pressure-volume work minimizes atrophy. We used a simpler approach to increase ventricular work, imposing aortic regurgitation on the transplant. We hypothesized that this would prevent atrophy and preserve left ventricular compliance. Methods We analyzed heterotopic transplants with aortic valvotomy and without aortic valvotomy (controls). Recipient native hearts served as separate controls. After 15 to 25 days, we measured cardiac wet weight, dry weight, and water content of all groups and measured echocardiographic left ventricular wall thickness and end-diastolic and end-systolic diameters in both transplant groups. Left ventricular volume infusions yielded pressure-volume data that we analyzed using regression methods. Results Aortic regurgitant transplants weighed more than control transplants (dry weight, 0.109 ± 0.013 g vs 0.097 ± 0.016 g; p = 0.020, 2-way analysis of variance), but all transplants weighed less than native hearts weighed ( p = 0.001). Control transplants were less compliant than regurgitant transplants ( p = 0.002), but the latter were similar to their own native hearts ( p = 0.34). Wall thickness decreased in regurgitant vs control transplants ( p = 0.020, Student’s t-test), but end-diastolic and end-systolic diameters increased ( p ≤ 0.001). Conclusions Aortic regurgitation in heterotopic transplants improves left ventricular compliance through chamber dilatation without preventing atrophy. Moderate acute aortic regurgitation affects ventricular remodeling more than it stimulates myocardial hypertrophy. Smaller end-diastolic diameter, greater wall thickness, and myocardial edema may explain decreased compliance in non-working transplants.

Left ventricular remodeling with age in normal men versus women: Novel insights using three-dimensional magnetic resonance imaging

Echocardiographic left ventricular (LV) wall thickness increases with age, suggesting LV hypertrophy. However, autopsy studies have shown no change, or even a decrease, in LV mass with age. With many pathologies, LV remodeling results in changes in ventricular shape. Age-associated LV shape change might explain this discrepancy, although this has not been studied. Magnetic resonance imaging (MRI) was used in 336 healthy, normotensive adults (mean age 56 ± 18 years; 200 women, 136 men) to measure LV mass, end-diastolic LV wall thickness, length, diameter, and shape. Echocardiographic LV mass was measured in a subset of 86 subjects by a standard algorithm. In women, LV wall thickness increased by 14% (r = 0.19, p <0.02), whereas LV length decreased by 9% (r = −0.26, p = 0.0006); LV diameter was unchanged. Thus, LV mass did not vary with age (r −0.04, p = 0.06) and the sphericity index decreased (r = −0.165, p <0.05). In men, LV wall thickness and diameter were unrelated to age, but there was an 11% decrease in LV length (r = −0.29, p = 0.003); therefore, there was an 11% decrease in LV mass (r = −0.20, p = 0.019) and a decrease in the sphericity index (r = −0.218, p <0.04). No change occurred in echocardiographic LV mass with age in either gender, although echocardiographic LV wall thickness increased in both. The left ventricle becomes more spherical with age in normal adults due to reduced LV length. In women, increased LV wall thickness offsets the decreasing LV length, whereas in men, LV wall thickness fails to compensate, resulting in decreased LV mass with age.