Lower Left Ventricular Fractional Shortening Research Articles

Prognostic impact of atrial fibrillation in patients with hypertrophic cardiomyopathy in a community-based Japanese cohort: results from Kochi RYOMA study

Abstract Background The prognostic impact of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM) is not fully elucidated. Purpose The aim of this study was to examine the prevalence and prognostic impact of AF in a prospectively assembled community-based HCM patient cohort in an aged Japanese community. Methods In 2004, we established a cardiomyopathy registration network in Kochi Prefecture, Japan, consisting of 9 hospitals, and finally 293 patients with HCM were followed. Results The ages at registration and at diagnosis were 63±14 and 56±16 years, respectively, and 197 patients (67%) were men. 86 patients (29%) showed AF. During follow-up period of 6.1±3.2 years, 44 patients died. In those patients, HCM-related deaths occurred in 23 patients with an annual mortality rate of 1.3%. Regarding HCM-related adverse events including HCM-related deaths, appropriate ICD discharge, heart failure admission and hospitalization for embolic events, a total of 77 cardiovascular events in 70 patients occurred. Multivariate analysis revealed that presence of AF, left ventricular (LV) outflow obstruction, NYHA functional class III, and lower LV fractional shortening at registration were significant predictors of these adverse events. During the follow-up period, additional 31 patients (11%) developed new-onset AF. Importantly, the incidence of HCM-related adverse events was significantly higher in patients with new AF observed from its onset compared with those with AF at registration (log-rank p=0.029) (Figure 1). Conclusions In an unselected HCM registry in an aged Japanese community, presence of AF, particularly new-onset AF, was associated with unfavorable clinical outcomes. AF is not just a marker of the disease stage but an important trigger of HCM-related adverse events. Figure 1 Funding Acknowledgement Type of funding source: None

Qishen Huanwu capsule reduces pirarubicin-induced cardiotoxicity in rats by activating the PI3K/Akt/mTOR pathway

One of the common adverse reactions to anthracyclines, a group of chemotherapeutics, is cardiotoxicity. Cancer patients receiving anthracycline-based chemotherapeutic regimens often discontinue treatment due to cardiotoxicity. How to prevent and reduce the cardiotoxicity of anthracyclines is one of the hot topics in the field of onco-cardiology. Traditional Chinese medicine can reduce the toxic side effects of chemotherapeutics. The present study aimed to investigate the protective effect of Qishen Huanwu capsule (QSHWC) on pirarubicin (THP)-induced myocardial injury in rats and the underlying mechanisms. Forty-eight male Sprague-Dawley (SD) rats were randomly divided into six groups: control group, THP, low-dose QSHWC, moderate-dose QSHWC, high-dose QSHWC, and LY294002 [phosphatidylinositol 3-kinase (PI3K) inhibitor] (n=8 each). Echocardiographic examination was performed to examine heart structure and function. Hematoxylin and eosin (HE) staining was conducted to examine histopathological changes in myocardial tissue. Immunofluorescence staining was carried out to examine the expression of the autophagosome-specific marker protein microtubule-associated protein 1 light chain 3 (LC3). Western blot was performed to analyze the expression of LC3-I, LC3-II, PI3K, phosphorylated (p)-PI3K, protein kinase B (Akt), p-Akt, mammalian target of rapamycin (mTOR), and p-mTOR. Compared with the control group, the THP group had a higher left ventricular end-systolic diameter (LVESD), lower left ventricular ejection fraction (LVEF), lower left ventricular fractional shortening (LVFS), and inferior heart function. In addition, compared with the control group, the THP group had significantly higher LC3 protein expression, a significantly higher LC3-II/LC3-I ratio (P<0.05), and significantly lower p-PI3K, p-Akt, and p-mTOR (P<0.05). QSHWC attenuated the THP-induced decline in heart function, downregulated LC3 protein in rat myocardial tissue, decreased the LC3-II/LC3-I ratio, and increased p-PI3K, p-Akt, and p-mTOR. In the LY294002 group, the above effects of QSHWC were reversed. QSHWC alleviated THP-induced myocardial injury. The underlying mechanism was related to the activation of the PI3K/Akt/mTOR pathway and the mitigation of the excessive autophagy of cardiomyocytes caused by THP.

Zinc Is Indispensable in Exercise-Induced Cardioprotection against Intermittent Hypoxia-Induced Left Ventricular Function Impairment in Rats.

In obstructive sleep apnea (OSA), recurrent obstruction of the upper airway leads to intermittent hypoxia (IH) during sleep, which can result in impairment of cardiac function. Although exercise can have beneficial effects against IH-induced cardiac dysfunction, the mechanism remains unclear. This study aimed to investigate the interactions of zinc and exercise on IH-triggered left ventricular dysfunction in a rat model that mimics IH in OSA patients. Nine-week-old male Sprague-Dawley rats were randomly assigned to either a control group (CON) or to a group receiving 10 weeks of exercise training (EXE). During weeks 9 and 10, half the rats in each group were subjected to IH for 8 h per day for 14 days (IHCON, IHEXE), whereas the remainder continued to breathe room air. Rats within each of the CON, IHCON, EXE, and IHEXE groups were further randomly assigned to receive intraperitoneal injections of either zinc chloride, the zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN), or injection vehicle only. IH induced a lower left ventricular fractional shortening, reduced ejection fraction, higher myocardial levels of inflammatory factors, increased levels oxidative stress, and lower levels of antioxidative capacity, all of which were abolished by zinc treatment. IHEXE rats exhibited higher levels of cardiac function and antioxidant capacity and lower levels of inflammatory factors and oxidative stress than IHCON rats; however, IHEXE rats receiving TPEN did not exhibit these better outcomes. In conclusion, zinc is required for protecting against IH-induced LV functional impairment and likely plays a critical role in exercise-induced cardioprotection by exerting a dual antioxidant and anti-inflammatory effect.

Role of Sodium-Hydrogen Exchanger-1 (NHE-1) in the Effect of Exercise on Intermittent Hypoxia-Induced Left Ventricular Dysfunction.

Intermittent hypoxia (IH) occurs frequently in patients with obstructive sleep apnoea and can cause ventricular dysfunction. However, whether myocardial inflammation and sodium-hydrogen exchanger-1 (NHE-1) expression play an important role in IH-induced ventricular dysfunction remains unclear. This study aimed to investigate whether short-term exercise provides a protective effect on IH-induced left ventricular (LV) function impairment. Male Sprague-Dawley rats were randomly assigned to 4 groups: control (CON), IH, exercise (EXE) or IH interspersed with EXE (IHEXE). IH rats were exposed to repetitive hypoxia/reoxygenation cycles (2%-6% O₂ for 2-5 s per 75 s, followed by 21% O₂ for 6 h/day) during the light phase for 12 consecutive days. EXE rats were habituated to treadmill running for 5 days, permitted 2 days of rest, and followed by 5 exercise bouts (30 m/min for 60 min on a 2% grade) on consecutive days during the dark phase. IHEXE rats were exposed to IH during the light phase interspersed with exercise programs during the dark phase on the same day. Cardiac function was quantified by echocardiographic evaluation. Myocardial levels of tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and NHE-1 were determined. IH rats showed LV dysfunction characterized by lower LV fractional shortening (LVFS%) and LV ejection fraction (LVEF%). LV dysfunction was associated with higher myocardial levels of TNF-α, IL-6 and NHE-1 mRNA and protein. These changes were not observed in IHEXE rats (P > 0.05 for all). EXE rats showed lower levels of NHE-1 protein than CON rats (P < 0.05). However, the levels of LVFS%, LVEF%, TNF-α and IL-6 protein and NHE-1 mRNA did not differ between EXE and CON rats (P > 0.05 for all). These data indicated that exercise may provide a protective effect on IH-induced LV dysfunction by attenuating IH-induced myocardial NHE-1 hyperactivity.

Is serum total bilirubin useful to differentiate cardioembolic stroke from other stroke subtypes?

Background:Previous studies have reported that the total bilirubin (TB) level is associated with coronary artery disease, heart failure and atrial fibrillation. These heart diseases can produce cardiogenic cerebral embolism and cause cardioembolic stroke. However, whether the serum TB could be a biomarker to differentiate cardioembolic stroke from other stroke subtypes is unclear.Methods:Our study consisted of 628 consecutive patients with ischaemic stroke. Various clinical and laboratory variables of the patients were analysed according to serum TB quartiles and stroke subtypes.Results:The higher TB quartile group was associated with atrial fibrillation, larger left atrium diameter, lower left ventricular fractional shortening and cardioembolic stroke (P < 0.001, P = 0.001, P = 0.033, P < 0.001, respectively). Furthermore, serum TB was a statistically significant independent predictor of cardioembolic stroke in a multivariable setting (Continuous, per unit increase OR = 1.091, 95%CI: 1.023–1.164, P = 0.008).Conclusions:Serum TB level was independently associated with cardioembolic stroke. The combination of clinical data and serum TB may be a feasible strategy to diagnose cardioembolic stroke in the acute phase.

Risk stratification at diagnosis for children with hypertrophic cardiomyopathy: an analysis of data from the Pediatric Cardiomyopathy Registry

Treatment of children with hypertrophic cardiomyopathy might be improved if the risk of death or heart transplantation could be predicted by risk factors present at the time of diagnosis. We analysed data from the Pediatric Cardiomyopathy Registry, which collected longitudinal data for 1085 children with hypertrophic cardiomyopathy from 1990 to 2009. Our goal was to understand how patient factors measured at diagnosis predicted the subsequent risk of the primary outcome of death or heart transplantation. The Kaplan-Meier method was used to calculate time-to-event rates from time of diagnosis to the earlier of heart transplantation or death for children in each subgroup. Cox proportional-hazards regression was used to identify univariable and multivariable predictors of death or heart transplantation within each causal subgroup. The poorest outcomes were recorded for the 69 children with pure hypertrophic cardiomyopathy with inborn errors of metabolism, for whom the estimated rate of death or heart transplantation was 57% (95% CI 44-69) at 2 years. Children with mixed functional phenotypes also did poorly, with rates of death or heart transplantation of 45% (95% CI 32-58) at 2 years for the 69 children with mixed hypertrophic and dilated cardiomyopathy and 38% (95% CI 25-51) at 2 years for the 58 children with mixed hypertrophic and restrictive cardiomyopathy. For children diagnosed with hypertrophic cardiomyopathy at younger than 1 year, the rate of death or transplantation was 21% (95% CI 16-27) at 2 years. For children diagnosed with hypertrophic cardiomyopathy and a malformation syndrome, the rate of death or transplantation was 23% (95% CI 12-34) at 2 years. Excellent outcomes were reported for the 407 children who were diagnosed with idiopathic hypertrophic cardiomyopathy at age 1 year or older, with a rate of death or heart transplantation of 3% (95% CI 1-5) at 2 years. The risk factors for poor outcomes varied according to hypertrophic cardiomyopathy subgroup, but they generally included young age, low weight, presence of congestive heart failure, lower left ventricular fractional shortening, or higher left ventricular end-diastolic posterior wall thickness or end-diastolic ventricular septal thickness at the time of cardiomyopathy diagnosis. For all hypertrophic cardiomyopathy subgroups, the risk of death or heart transplantation was significantly increased when two or more risk factors were present and also as the number of risk factors increased. In children with hypertrophic cardiomyopathy, the risk of death or heart transplantation was greatest for those who presented as infants or with inborn errors of metabolism or with mixed hypertrophic and dilated or restrictive cardiomyopathy. Risk stratification by subgroup of cardiomyopathy, by characteristics such as low weight, congestive heart failure, or abnormal echocardiographic findings, and by the presence of multiple risk factors allows for more informed clinical decision making and prognosis at the time of diagnosis. US National Institutes of Health and Children's Cardiomyopathy Foundation.

Outcomes in children with Noonan syndrome and hypertrophic cardiomyopathy: A study from the Pediatric Cardiomyopathy Registry

Studies of cardiomyopathy in children with Noonan syndrome (NS) have been primarily small case series or cross-sectional studies with small or no comparison groups. We used the Pediatric Cardiomyopathy Registry database to compare the survival experience of children with NS and hypertrophic cardiomyopathy (HCM) with children with idiopathic or familial HCM and to identify clinical and echocardiographic predictors of clinical outcomes. Longitudinal data in 74 children with NS and HCM and 792 children with idiopathic or familial isolated HCM were compared. Children with NS were diagnosed with HCM before 6 months old more often (51%) than children with HCM (28%) and were more likely to present with congestive heart failure (CHF) (24% vs 9%). The NS cohort had lower crude survival than the group with other HCM (P = .03), but survival did not differ after adjustment for CHF and age at diagnosis. Within the NS cohort (1-year survival 78%), a diagnosis of HCM before age 6 months with CHF resulted in 31% 1-year survival. Lower height-for-age z score (hazard ratio 0.26, P = .005) in place of CHF and lower left ventricular fractional shortening z score (hazard ratio 0.79, P = .04) also independently predicted mortality. Patients with NS with HCM have a worse risk profile at presentation compared with other children with HCM, resulting in significant early mortality (22% at 1 year). Decreased height-for-age and lower, although still supranormal, left ventricular fractional shortening z score are independent predictors of mortality in patients with NS with HCM. Such patients should have an aggressive therapeutic approach including potential listing for cardiac transplantation.

ABCC1 polymorphisms in anthracycline‐induced cardiotoxicity in childhood acute lymphoblastic leukaemia

Anthracyclines are potent cytostatic drugs, the correct dosage being critical to avoid possible cardiac side effects. ABCC1 [ATP-binding cassette, sub-family C, member 1; also denoted as MRP1 (multidrug resistance-associated protein 1)] is expressed in the heart and takes part in the detoxification and protection of cells from the toxic effects of xenobiotics, including anthracyclines. Our objective was to search for associations between LV (left ventricular) function and single-nucleotide polymorphisms of the ABCC1 gene in children receiving anthracycline chemotherapy. Data of 235 paediatric patients with acute lymphoblastic leukaemia was analysed. Patients were followed-up by echocardiography (median follow-up 6.3 years). Nine polymorphisms in the ABCC1 gene were genotyped. The ABCC1 rs3743527TT genotype and rs3743527TT–rs246221TC/TT genotype combination were associated with lower LVFS (left ventricular fractional shortening) after chemotherapy. The results suggest that genetic variants in the ABCC1 gene influence anthracycline-induced LV dysfunction.

Influence of Myocardial Fibrosis on Left Ventricular Hypertrophy in Patients with Symptomatic Severe Aortic Stenosis

Aim: It was the aim of our study to determine whether myocardial fibrosis influences physiologic or non-physiologic left ventricular (LV) hypertrophy in severe aortic stenosis. Methods: Myocardial fibrosis was evaluated using specimens taken from the ventricular septum in 79 patients submitted to aortic valve replacement because of symptomatic aortic stenosis. Patients were considered to have physiologic LV hypertrophy if end-systolic wall stress, evaluated by echocardiography, was <90 kdyn/cm², while those with end-systolic wall stress >90 kdyn/cm² were considered to have non-physiologic hypertrophy. Results: Fibrosis tissue mass index was significantly inversely related with LV fractional shortening and directly related with LV diastolic and systolic diameter and LV mass index (LVMI). Patients with non-physiologic hypertrophy (n = 24) had a higher LVMI due to larger LV diastolic and systolic diameters with thinner wall, resulting in lower relative wall thickness. These patients had a higher fibrosis tissue mass index and impaired LV systolic and diastolic functions, as suggested by lower LV fractional shortening and higher mean wedge pressure. At follow-up of 7.4 ± 2.1 months, the LVMI and New York Heart Association class remained higher in patients with non-physiologic hypertrophy. Conclusions: Our study suggests a different quality of hypertrophies in patients with aortic stenosis, where myocardial fibrosis seems to be the critical abnormality that differentiates adaptive from maladaptive response to increased afterload.

Systemic maternal inflammation and neonatal hyperoxia induces remodeling and left ventricular dysfunction in mice.

AimsThe impact of the neonatal environment on the development of adult cardiovascular disease is poorly understood. Systemic maternal inflammation is linked to growth retardation, preterm birth, and maturation deficits in the developing fetus. Often preterm or small-for-gestational age infants require medical interventions such as oxygen therapy. The long-term pathological consequences of medical interventions on an immature physiology remain unknown. In the present study, we hypothesized that systemic maternal inflammation and neonatal hyperoxia exposure compromise cardiac structure, resulting in LV dysfunction during adulthood.Methods and ResultsPregnant C3H/HeN mice were injected on embryonic day 16 (E16) with LPS (80 µg/kg; i.p.) or saline. Offspring were placed in room air (RA) or 85% O2 for 14 days and subsequently maintained in RA. Cardiac echocardiography, cardiomyocyte contractility, and molecular analyses were performed. Echocardiography revealed persistent lower left ventricular fractional shortening with greater left ventricular end systolic diameter at 8 weeks in LPS/O2 than in saline/RA mice. Isolated cardiomyocytes from LPS/O2 mice had slower rates of contraction and relaxation, and a slower return to baseline length than cardiomyocytes isolated from saline/RA controls. α-/β-MHC ratio was increased and Connexin-43 levels decreased in LPS/O2 mice at 8 weeks. Nox4 was reduced between day 3 and 14 and capillary density was lower at 8 weeks of life in LPS/O2 mice.ConclusionThese results demonstrate that systemic maternal inflammation combined with neonatal hyperoxia exposure induces alterations in cardiac structure and function leading to cardiac failure in adulthood and supports the importance of the intrauterine and neonatal milieu on adult health.

Competing Risks for Death and Cardiac Transplantation in Children With Dilated Cardiomyopathy

Background Pediatric dilated cardiomyopathy (DCM) is the leading indication for heart transplantation after 1 year of age. Risk factors by etiology at clinical presentation have not been determined separately for death and transplantation in population-based studies. Competing risks analysis may inform patient prioritization for transplantation listing. Methods and Results The Pediatric Cardiomyopathy Registry enrolled 1731 children diagnosed with DCM from 1990 to 2007. Etiologic, demographic, and echocardiographic data collected at diagnosis were analyzed with competing risks methods stratified by DCM etiology to identify predictors of death and transplantation. For idiopathic DCM (n=1192), diagnosis after 6 years of age, congestive heart failure, and lower left ventricular (LV) fractional shortening z score were independently associated with both death and transplantation equally. In contrast, increased LV end-diastolic dimension z score was associated only with transplantation, whereas lower height-for-age z score was associated only with death. For neuromuscular disease (n=139), lower LV fractional shortening was associated equally with both end points, but increased LV end-diastolic dimension was associated only with transplantation. The risks of death and transplantation were increased equally for older age at diagnosis, congestive heart failure, and increased LV end-diastolic dimension among those with myocarditis (n=272) and for congestive heart failure and decreased LV fractional shortening among those with familial DCM (n=79). Conclusions Risk factors for death and transplantation in children varied by DCM etiology. For idiopathic DCM, increased LV end-diastolic dimension was associated with increased transplantation risk but not mortality. Conversely, short stature was significantly related to death but not transplantation. These findings may present an opportunity to improve the transplantation selection algorithm.

In- and outpatients with noncompaction: Differences in cardiac and neuromuscular co-morbidity

Background and methods The prognosis of patients with left ventricular hypertrabeculation/noncompaction (LVHT) is controversial. LVHT is associated with neuromuscular disorders (NMD) and diagnosed echocardiographically in in- as well as outpatients. We compared cardiologic and neurologic findings and mortality in LVHT-patients according to their diagnosis established as in- or outpatients. Results Among 113 patients (33 females, mean-age 53 years), 91 were investigated neurologically. Fifty-nine inpatients were older (55 versus 50 years, p < 0.05), more frequently referred because of heart failure (73 versus 37%, p < 0.001), had more often diabetes (24 versus 7%, p < 0.05), heart failure (81 versus 57%, p < 0.01), a lower left-ventricular fractional-shortening (21 versus 26%, p < 0.05) and more extensive LVHT (1.7 versus 1.5 affected walls, p < 0.05). Fifty-four outpatients were referred more often because of chest-pain (33 versus 12%, p < 0.01), myopathy (13 versus 2%, p < 0.05), were more often neurologically normal (20 versus 7%, p < 0.05) or had a specific NMD (28 versus 12%, p < 0.05). During a mean follow-up of 3.8 years, mortality was 5.8%/year. Inpatients had a higher mortality (12.1 versus 2.1%/year, p = 0.0002) and a shorter time between LVHT-diagnosis and death (1.7 versus 4.6 years, p = 0.0197) than outpatients. Conclusions Outpatients with LVHT have a better prognosis than inpatients. Inpatients with LVHT should be closely monitored.

Left Ventricular Morphology and Systolic Function in Sleep-Disordered Breathing

Whether sleep-disordered breathing (SDB) is a risk factor for left ventricular (LV) hypertrophy and dysfunction is controversial. We assessed the relation of SDB to LV morphology and systolic function in a community-based sample of middle-aged and older adults. The present study was a cross-sectional observational study of 2058 Sleep Heart Health Study participants (mean age 65+/-12 years; 58% women; 44% ethnic minorities) who had technically adequate echocardiograms. A polysomnographically derived apnea-hypopnea index (AHI) and hypoxemia index (percent of sleep time with oxyhemoglobin saturation < 90%) were used to quantify SDB severity. LV mass index was significantly associated with both AHI and hypoxemia index after adjustment for age, sex, ethnicity, study site, body mass index, current and prior smoking, alcohol consumption, systolic blood pressure, antihypertensive medication use, diabetes mellitus, and prevalent myocardial infarction. Adjusted LV mass index was 41.3 (SD 9.90) g/m(2.7) in participants with AHI < 5 (n=957) and 44.1 (SD 9.90) g/m(2.7) in participants with AHI > or = 30 (n=84) events per hour. Compared with participants with AHI < 5, those with AHI > or = 30 had an adjusted odds ratio of 1.78 (95% confidence interval 1.14 to 2.79) for LV hypertrophy. A higher AHI and higher hypoxemia index were also associated with larger LV diastolic dimension and lower LV ejection fraction, with a trend toward lower LV fractional shortening. LV wall thickness was significantly associated with the hypoxemia index but not with AHI. Left atrial diameter was not associated with either SDB measure. In a community-based cohort, SDB is associated with echocardiographic evidence of increased LV mass and reduced LV systolic function.

Abstract 1271: IKKβ/NF-κB Pathway Protects Hearts from Hemodynamic Stress Mediated through Regulating MnSOD Expression

Objectives: We have previously reported that NF-κB contributes to GPCR agonist-induced hypertrophy in cultured cardiomyocytes. However, the in vivo role of this pathway in the pathogenesis of cardiac remodeling remains to be elucidated. Although IκB kinase β (IKKβ)/NF-κB pathway is a major negative regulator of cell death, it can sensitize cells to death-inducing stimuli in some instances, thus it can be either anti- or pro-apoptotic. In this study, we aimed to clarify the role of IKKβ/NF-κB signaling in cardiac remodeling using cardiac-specific IKKβ deficient mice. Methods and Results: We crossed mice bearing an IKK β flox allele with mice expressing the Cre recombinase under the control of the myosin light chain 2v promoter ( MLC2v-Cre +/− ) to generate IKK β flox/flox ; MLC2v-Cre +/− mice (conditional knockout:CKO). Then, CKO mice (n=14) and control littermates bearing IKK β flox/flox (CTRL, n=14) were subjected to pressure overload by means of transverse aortic constriction (TAC). EMSA analysis revealed NF-κB DNA binding activity after TAC had attenuated in CKO hearts. One week after TAC, echocardiography showed significantly lower left ventricular fractional shortening (26.9±2.7% vs. 41.4±0.9%, p&lt;0.01), and higher left ventricular end-diastolic dimension (4.02±0.14 mm vs. 3.47±0.08 mm, p&lt;0.01) and lung weight/body weight ratio (11.1±1.4 vs. 5.5±0.1, p&lt;0.01) in CKO mice compared with CTRL mice, indicating the development of heart failure in CKO mice. Number of apoptotic cells had increased in CKO hearts after TAC, suggesting that the enhanced apoptosis is a cause for heart failure. The expression levels of MnSOD mRNA and protein after TAC, which is one of NF-κB target genes, were significantly lower in CKO than those in CTRL mice. As a consequence, oxidative stress and JNK activation in CKO hearts after TAC had significantly increased compared with those in CTRL heart, suggesting that increased oxidative stress and enhanced JNK activity resulted in cardiomyocyte apoptosis in CKO hearts. Conclusion: These results show that IKKβ/NF-κB pathway in cardiomyocyte plays a protective role mediated through attenuation of oxidative stress and JNK activation in response to pressure overload.

Incidence, Causes, and Outcomes of Dilated Cardiomyopathy in Children

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and cause of cardiac transplantation in children. However, the epidemiology and clinical course of DCM in children are not well established. To provide a detailed description of the incidence, causes, outcomes, and related risk factors for DCM in children. Longitudinal study based on a population-based, prospective cohort of children diagnosed as having DCM since January 1, 1996, at 89 pediatric cardiac centers and a retrospectively collected cohort of patients seen primarily at large tertiary care centers in North America and who had diagnoses between January 1, 1990, and December 31, 1995, and were enrolled through February 2003. A total of 1426 children from the United States and Canada diagnosed as having DCM at younger than 18 years. Primary DCM was determined by strict echocardiographic and/or pathologic criteria. Patients with disease due to endocrine, immunologic, drug toxicity, and other causes were excluded. Annual incidence per 100,000 children; mortality; cardiac transplantation. The annual incidence of DCM in children younger than 18 years was 0.57 cases per 100,000 per year overall. The annual incidence was higher in boys than in girls (0.66 vs 0.47 cases per 100,000; P<.001), in blacks than in whites (0.98 vs 0.46 cases per 100,000; P<.001), and in infants (<1 year) than in children (4.40 vs 0.34 cases per 100,000; P<.001). The majority of children (66%) had idiopathic disease. The most common known causes were myocarditis (46%) and neuromuscular disease (26%). The 1- and 5-year rates of death or transplantation were 31% and 46%, respectively. Independent risk factors at DCM diagnosis for subsequent death or transplantation were older age, congestive heart failure, lower left ventricular fractional shortening Z score, and cause of DCM (P<.001 for all). In children, DCM is a diverse disorder with outcomes that depend largely on cause, age, and heart failure status at presentation. Race, sex, and age affect the incidence of disease. Most children do not have a known cause of DCM, which limits the potential for disease-specific therapies.

Cardiologic and neurologic findings in left ventricular hypertrabeculation/noncompaction relating to echocardiographic indication

Background Left-ventricular hypertrabeculation/noncompaction (LVHT) is characterized by prominent trabeculations and intertrabecular recesses. LVHT is usually diagnosed if a patient is referred for echocardiography. The study assessed if cardiologic and neurologic findings differ relating to indication for echocardiography. Methods Included were patients in whom LVHT was diagnosed in one echocardiographic laboratory between June 1995 and December 2005. All patients underwent a cardiologic examination and were invited for a neurological investigation. Results LVHT was diagnosed in 93/35,181 patients(26 female, 53 ± 15 years). Heart failure was the most frequent indication ( n = 49), followed by chest pain ( n = 21), syncope ( n = 8), search for cardiac involvement in myopathy ( n = 7), stroke or embolism ( n = 3), arterial hypertension ( n = 3) and screening of LVHT patients' relatives ( n = 2). Patients with the indication “heart failure” were older than patients with other indications (59.4 ± 13.1 versus 44.9 ± 12.9 years, p < 0.001), had more often a neuromuscular disorder of unknown etiology (53% versus 32%, p < 0.05), exertional dyspnoea (96% versus 32%, p < 0.001), edema (25% versus 7%, p < 0.05) and advanced heart failure (NYHA III: 41% versus 11%, p < 0.01; NYHA IV: 29% versus 9%, p < 0.05), suffered less often from arterial hypertension (22% versus 41%, p < 0.05), angina pectoris (14% versus 34%, p < 0.05) and palpitations or syncope (10% versus 30%, p < 0.05). Patients with the indication “heart failure” had less frequent normal ECG than patients with other indications (2% versus 18%, p < 0.01), had more frequent ≥ 2 ECG abnormalities (57% versus 36%, p < 0.05), left bundle branch block (29% versus 9%, p < 0.05), a larger left-ventricular enddiastolic diameter (69.9 ± 9.7 versus 57.4 ± 12.2 mm, p < 0.001), a lower left-ventricular fractional shortening (16.9 ± 6.1% versus 31.1 ± 11.5%, p < 0.001) and more often valvular abnormalities (76% versus 30%, p < 0.001). Location and extension of LVHT did not differ between indication groups. Conclusion Echocardiographers should be aware of LVHT in any indication for echocardiography.

Left Ventricular Remodeling of Hypertrophic Cardiomyopathy Longitudinal Observation in a Rural Community

The purpose of the present study was to assess the clinical long-term course of hypertrophic cardiomyopathy (HCM) in a rural Japanese cohort. A total of 137 consecutive HCM patients (mean age at diagnosis: 52+/-13 years) were enrolled. During a follow-up period of 11.4+/-5.7 years, 28 patients died of HCM-related causes. Eleven patients died suddenly, 10 died of progressive heart failure, 6 died of stroke associated with atrial fibrillation and 1 died of a postoperative complication of alcohol septal ablation. For the overall study group, 5-, 10- and 15-year cumulative survival rates were 91%, 88% and 79%, respectively. Although sudden death was the predominant cause of HCM-related death during the follow-up period of <10 years, heart failure death increased after follow-up period of >10 years. Fifteen (13%) of 114 patients who had follow-up echocardiography became ;end-stage' HCM and 8 patients died of severe and refractory heart failure. They already showed minimally dilated left ventricular (LV) dimension and lower LV fractional shortening at initial evaluation. Although HCM patients in a Japanese rural community showed relatively benign clinical course (the same as cohorts in the developed world), heart failure death because of LV remodeling became equally important to sudden death when they were followed for more than 10 years.

Age-dependency of cardiac and neuromuscular findings in left ventricular noncompaction

Background Left ventricular hypertrabeculation/noncompaction (LVHT) is a cardiac abnormality characterized by prominent trabeculations and intertrabecular recesses, and frequently associated with neuromuscular disorders (NMD). Initially described in children and young adults, LVHT has been found also in elderly. Aim of the study was to assess the age-dependency of clinical, electrocardiographic (ECG) and echocardiographic findings, and whether they differ according to the neurologic diagnosis. Methods and results In 86 patients LVHT was diagnosed echocardiographically between June 1995 and December 2004 (65 male, median age 52 years, range 14–94). All patients underwent a baseline cardiologic investigation and were invited for a neurologic investigation. A specific NMD was diagnosed in 21 (metabolic myopathy, n = 14; Leber's hereditary optic neuropathy, n = 3; myotonic dystrophy, n = 2; Becker muscular dystrophy, n = 1; Duchenne muscular dystrophy, n = 1), a NMD of unknown etiology in 32. The neurologic investigation was normal in 13 and was refused by 20 patients. Patients above median age had more often heart failure (43% versus 95%, p < 0.02) and valvular abnormalities (71% versus 36%, p < 0.02) than below median age. Patients > 71 years had more often exertional dyspnoea (39% versus 81%, p < 0.02), left bundle branch block (9% versus 38%, p = 0.031), larger left-ventricular enddiastolic diameters (68 versus 60 mm, p < 0.02) and a lower left-ventricular fractional shortening than patients < 34 years (18% versus 29%, p < 0.02). No age-dependency was detected regarding location and extension of LVHT and the neurologic diagnosis. Conclusion There is no age-dependent typical pattern of LVHT regarding clinical, echocardiographic and neurologic findings. Echocardiographers should be aware of this cardiac abnormality when investigating patients of any age.

Impact of diabetes on cardiac structure and function: the strong heart study.

Whether diabetes mellitus (DM) adversely affects left ventricular (LV) structure and function independently of increases in body mass index (BMI) and blood pressure is controversial. Echocardiography was used in the Strong Heart Study, a study of cardiovascular disease in American Indians, to compare LV measurements between 1810 participants with DM and 944 with normal glucose tolerance. Participants with DM were older (mean age, 60 versus 59 years), had higher BMI (32.4 versus 28.9 kg/m(2)) and systolic blood pressure (133 versus 124 mm Hg), and were more likely to be female, to be on antihypertensive treatment, and to live in Arizona (all P<0.001). In analyses adjusted for covariates, women and men with DM had higher LV mass and wall thicknesses and lower LV fractional shortening, midwall shortening, and stress-corrected midwall shortening (all P<0.002). Pulse pressure/stroke volume, a measure of arterial stiffness, was higher in participants with DM (P<0.001 independent of confounders). Non-insulin-dependent DM has independent adverse cardiac effects, including increased LV mass and wall thicknesses, reduced LV systolic chamber and myocardial function, and increased arterial stiffness. These findings identify adverse cardiovascular effects of DM, independent of associated increases in BMI and arterial pressure, that may contribute to cardiovascular events in diabetic individuals.

Tolerability and efficacy of carvedilol in patients with New York Heart Association class IV heart failure

OBJECTIVESThe purpose of this study was to assess the tolerability and efficacy of carvedilol in patients with New York Heart Association (NYHA) functional class IV symptoms.BACKGROUNDCarvedilol, a nonselective beta-adrenergic blocking drug with alpha-adrenergic blocking and antioxidant properties, has been shown to improve left ventricular function and clinical outcome in patients with mild to moderate chronic heart failure.METHODSWe retrospectively analyzed the outcomes of 230 patients with heart failure treated with carvedilol who were stratified according to baseline functional class: 63 patients were NYHA class IV and 167 were NYHA class I, II or III. Carvedilol was commenced at 3.125 mg b.i.d. and titrated to 25 mg b.i.d. as tolerated. Patients with class IV symptoms were older (p = 0.03), had lower left ventricular fractional shortening (p < 0.001), had lower six-min walk distance (p < 0.001) and were receiving more heart failure medications at baseline compared with less symptomatic patients.RESULTSNonfatal adverse events while taking carvedilol occurred more frequently in class IV patients (43% vs. 24%, p < 0.0001), and more often resulted in permanent withdrawal of the drug (25% vs. 13%, p < 0.01). Thirty-seven (59%) patients who were NYHA class IV at baseline had improved by one or more functional class at 3 months, 8 (13%) were unchanged and 18 (29%) had deteriorated or died. Among the less symptomatic group, 62 (37%) patients had improved their NYHA status at 3 months, 73 (44%) were unchanged and 32 (19%) had deteriorated or died. The differences in symptomatic outcome at three months between the two groups were statistically significant (p = 0.001, chi-square analysis). Both groups demonstrated similar significant improvements in left ventricular dimensions and systolic function.CONCLUSIONSPatients with chronic NYHA class IV heart failure are more likely to develop adverse events during initiation and dose titration when compared with less symptomatic patients but are more likely to show symptomatic improvement in the long term. We conclude that carvedilol is a useful adjunctive therapy for patients with NYHA class IV heart failure; however, they require close observation during initiation and titration of the drug.