Onset Of Cardiac Disease Research Articles

Fat Mass is Associated with Subclinical Left Ventricular Systolic Dysfunction in Patients with Type 2 Diabetes Mellitus Without Established Cardiovascular Diseases.

Left ventricular global longitudinal strain (GLS) is considered to be the first marker of diabetes mellitus-related subclinical cardiac dysfunction, but whether it is attributable to fat mass and distribution remains uncertain. In this study, we explored whether fat mass, especially fat mass in the android area, is associated with subclinical systolic dysfunction before the onset of cardiac disease. We conducted a single-center prospective cross-sectional study between November 2021 and August 2022 on inpatients of the Department of Endocrinology, Nanjing Drum Tower Hospital. We included 150 patients aged 18-70 years with no signs, symptoms, or history of clinical cardiac disease. Patients were evaluated with speckle tracking echocardiography and dual energy X-ray absorptiometry. The cutoff values for subclinical systolic dysfunction were set at a global longitudinal strain (GLS) < 18%. After adjusting for sex and age, patients with GLS < 18% had a higher mean (± standard deviation) fat mass index (8.06 ± 2.39 vs. 7.10 ± 2.09kg/m2, p = 0.02), higher mean trunk fat mass (14.9 ± 4.9 vs. 12.8 ± 4.3kg, p = 0.01), and higher android fat mass (2.57 ± 1.02 vs. 2.18 ± 0.86kg, p = 0.02) than those in the GLS ≥ 18%. Partial correlation analysis showed that the fat mass index, truck fat mass, and android fat mass were negatively correlated with GLS after adjusting for sex and age (all p < 0.05). Adjusted for traditional cardiovascular metabolic factors, fat mass index (odds ratio [OR] 1.27, 95% confidence interval [CI] 1.05-1.55, p = 0.02), trunk fat mass (OR 1.13, 95% CI 1.03-1.24, p = 0.01), and android fat mass (OR 1.77, 95% CI 1.16-2.82, p = 0.01) were independent risk factors for GLS < 18%. Among patients with type 2 diabetes mellitus without established clinical cardiac disease, fat mass, especially android fat mass, was associated with subclinical systolic dysfunction independently of age and sex.

Cardiac pericytes may contribute to heart disease

Cardiovascular diseases which are the leading cause of death worldwide are promoted by well-known risk factors that include high blood pressure, age, sex, diabetes and/or obesity. Pericytes are mural cells wrapped around microvessels in many organs. They are mostly described as essential for microvascular integrity in the brain and retina. While the detrimental effects of cardiovascular risk factors on endothelial cells have been extensively studied, little is known about their impact on the biology of pericytes, especially in the heart. To determine how cardiac pericytes are modified by some cardiovascular risk factors. To do so, we used mice that were exposed to a high-fat diet (HFD) only to recapitulate obesity, to a HFD together with low dose-streptozotocin injections to mimic type 2 diabetes or to a HFD and L-NAME to recapitulate obesity with a mild hypertension. Mice were sacrificed 3 or 6 months after establishing these risk factors for histological and gene expression analyses. In mice exposed to the HFD + L-NAME regimen for 3 months, the percentage of capillaries covered by pericytes was not modified. However their phenotype appeared to be modified. Indeed, we isolated pericytes (CD31–, CD146+ cells) in the heart of both HFD L-NAME fed mice and control mice using magnetic beads and performed a bulk RNA-sequencing analysis on these cells which identified 3 genes of which the expression was significantly different in the 2 groups. In particular, Angiopoietin-like 4 mRNA expression was increased in the pericytes of HFD + L-NAME fed mice. This protein plays an important role in the regulation of lipid metabolism which makes it attractive to explore. In mice exposed to either HFD alone of HFD + streptozotocin for 6 months, the percentage of capillaries covered by pericytes was significantly diminished suggesting pericyte death. Cardiovascular risk factors, such as obesity and diabetes, may change the phenotype and/or the number of pericytes in the heart suggesting that these cells, known to be critical for microvascular integrity, could contribute to the onset of cardiac diseases.

Advanced Echocardiographic Analysis in Medium-Term Follow-Up of Children with Previous Multisystem Inflammatory Syndrome.

Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory disease related to SARS-CoV2 infection, with frequent cardiovascular involvement in the acute setting. The aim of the study was to evaluate the cardiac function at 6 months. Thirty-two patients diagnosed with MIS-C were enrolled and underwent advanced echocardiogram at discharge and at 6 months. According to the left ventricular ejection fraction (LVEF) at admission, the patients were divided into group A (LVEF < 45%) and group B (LVEF ≥ 45%) and the follow-up results were compared. At discharge, all patients had normal LV and RV systolic function (LVEF 61 ± 4.4%, LV global longitudinal strain −22.1%, TAPSE 20.1mm, s’ wave 0.13m/s, RV free wall longitudinal strain −27.8%) with normal LV diastolic function (E/A 1.5, E/e’ 5.7, and left atrial strain 46.5%) and no significant differences at 6 months. Compared to group B, the group A patients showed a reduced, even if normal, LV global longitudinal strain at discharge (−21.1% vs. −22.6%, p-value 0.02), but the difference was no longer significant at the follow-up. Patients with MIS-C can present with depressed cardiac function, but if treated, the cardiac function recovered without late onset of cardiac disease. This favorable result was independent of the severity of acute LV dysfunction.

Infection with SARS-CoV-2 variant B.1.1.7 detected in a group of dogs and cats with suspected myocarditis.

BackgroundDomestic pets can contract severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection; however, it is unknown whether the UK B.1.1.7 variant can more easily infect certain animal species or increase the possibility of human‐to‐animal transmission.MethodsThis is a descriptive case series reporting SARS‐CoV‐2 B.1.1.7 variant infections in a group of dogs and cats with suspected myocarditis.ResultsThe study describes the infection of domestic cats and dogs by the B.1.1.7 variant. Two cats and one dog were positive to SARS‐CoV‐2 PCR on rectal swab, and two cats and one dog were found to have SARS‐CoV‐2 antibodies 2–6 weeks after they developed signs of cardiac disease. Many owners of these pets had developed respiratory symptoms 3–6 weeks before their pets became ill and had also tested positive for COVID‐19. Interestingly, all these pets were referred for acute onset of cardiac disease, including severe myocardial disorders of suspected inflammatory origin but without primary respiratory signs.ConclusionsThese findings demonstrate, for the first time, the ability for pets to be infected by the B.1.1.7 variant and question its possible pathogenicity in these animals.

The Role of Proteostasis Derailment in Cardiac Diseases

The incidence and prevalence of cardiac diseases, which are the main cause of death worldwide, are likely to increase because of population ageing and changes in lifestyle. Prevailing theories about the mechanisms of cardiac disease onset feature the gradual derailment of cellular protein homeostasis (proteostasis) and loss of the protein quality control as central factors. In the heart, loss of protein patency, due to flaws in design (genetically) or environmentally-induced wear and tear, may overwhelm protein quality control, thereby triggering derailment of proteostasis and contributing to cardiac disease onset.

A thermodynamic transient cross-bridge model for prediction of contractility and remodelling of the ventricle

Cardiac hypertrophy is an adaption of the heart to a change in cardiovascular loading conditions. The current understanding is that progression may be stress or strain driven, but the multi-scale nature of the cellular remodelling processes have yet to be uncovered. In this study, we develop a model of the contractile left ventricle, with the active cell tension described by a thermodynamically motivated cross-bridge cycling model. Simulation of the transient recruitment of myosin results in correct patterns of ventricular pressure predicted over a cardiac cycle. We investigate how changes in tissue loading and associated deviations in transient force generation can drive restructuring of cellular myofibrils in the heart wall. Our thermodynamic framework predicts in-series sarcomere addition (eccentric remodelling) in response to volume overload, and sarcomere addition in parallel (concentric remodelling) in response to valve and signalling disfunction. This framework provides a significant advance in the current understanding of the fundamental sub-sarcomere level biomechanisms underlying cardiac remodelling. Simulations reveal that pathological tissue loading conditions can significantly alter actin-myosin cross-bridge cycling over the course of the cardiac cycle. The resultant variation in sarcomere stress pushes an imbalance between the internal free energy of the myofibril and that of unbound contractile proteins, initiating remodelling. The link between cross-bridge thermodynamics and myofibril remodelling proposed in this study may significantly advance current understanding of cardiac disease onset.

Incidence and Onset of Severe Cardiac Events After Radiotherapy for Esophageal Cancer.

Late cardiotoxicity related to radiotherapy (RT) in breast cancer and Hodgkin's lymphoma has been well-reported. However, the relatively higher cardiac dose exposure for esophageal cancer (EC) may result in the earlier onset of cardiac diseases. In this report, we examined the incidence, onset, and long-term survival outcomes of high-grade cardiac events after RT in a large cohort of patients with EC. Between March 2005 and August 2017, a total of 479 patients with EC from a prospectively maintained institutional database at The University of Texas MD Anderson Cancer Center were analyzed. All patients were treated with either intensity-modulated RT or proton beam therapy, either preoperatively or definitively. We focused on any grade 3 or higher (G3+) cardiac events according to the Common Terminology Criteria for Adverse Events, version 5.0. G3+ cardiac events occurred in 18% of patients at a median of 7 months with a median follow-up time of 76 months. Preexisting cardiac disease (p= 0.001) and radiation modality (intensity-modulated RT versus proton beam therapy) (p= 0.027) were significantly associated with G3+ cardiac events. Under multivariable analysis, the mean heart dose, particularly of less than 15 Gy, was associated with reduced G3+ events. Furthermore, G3+ cardiac events were associated with worse overall survival (p= 0.041). Severe cardiac events were relatively common in patients with early onset EC after RT, especially those with preexisting cardiac disease and higher radiation doses to the heart. Optimal treatment approaches should be taken to reduce cumulative doses to the heart, especially for patients with preexisting cardiac disease.

Evaluating anthracycline cardiotoxicity associated single nucleotide polymorphisms in a paediatric cohort with early onset cardiomyopathy

BackgroundAnthracyclines are a mainstay of chemotherapy. However, a relatively frequent adverse outcome of anthracycline treatment is cardiomyopathy. Multiple genetic studies have begun to dissect the complex genetics underlying cardiac sensitivity to the anthracycline drug class. A number of single nucleotide polymorphisms (SNPs) have been identified to be in linkage disequilibrium with anthracycline induced cardiotoxicity in paediatric populations.MethodsHere we screened for the presence of SNPs resulting in a missense coding change in a cohort of children with early onset chemotherapy related cardiomyopathy. The SNP identity was evaluated by Sanger sequencing of PCR amplicons from genomic DNA of patients with anthracycline related cardiac dysfunction.ResultsAll of the published SNPs were observed within our patient group. There was no correlation between the number of missense variants an individual carried with severity of disease. Furthermore, the time to cardiac disease onset post-treatment was not greater in those individuals carrying a high load of SNPs resulting from missense variants.ConclusionsWe conclude that previously identified missense SNPs are present within a paediatric cohort with early onset heart damage induced by anthracyclines. However, these SNPs require further replication cohorts and functional validation before being deployed to assess anthracycline cardiotoxicity risk in the clinic.

Les peptides natriurétiques en dialyse : de la théorie à la pratique

Cardiologists and emergency-wards physicians are used to check natriuretic peptides serum level, mainly B-type natriuretic peptide and N-terminal pro-Brain natriuretic peptide for acute cardiac failure diagnosis. Due to their accumulation in chronic kidney disease and their elimination by dialysis, natriuretic peptides sampling remains debatable in chronic kidney disease patients. In dialysis patients, high natriuretic peptides values are associated with mortality, left ventricular hypertrophy and cardiac failure. However, a single value cannot provide a reliable diagnosis. Our clinical practice is as follows: First, we prefer B-type natriuretic peptide to N-terminal pro-Brain natriuretic peptide because of its shorter half-life, with less impact of renal function and dialysis, making its interpretation easier in case of advanced chronic kidney disease or in dialysis patients; second, we define a reference value of B-type natriuretic peptide at dry weight from serial measurements; third, the B-type natriuretic peptide changes are interpreted according to extracellular fluid and cardiac status, but also from the arteriovenous fistula blood flow. In stable dialysis patients, B-type natriuretic peptide is sampled monthly and weekly in unstable patients. We illustrate our experience using clinical cases of overhydration, new cardiac disease onset, hypovolemia and arteriovenous fistula with high blood flow. Longitudinal follow-up of B-type natriuretic peptide is an important advance in dialysis patients in order to detect and treat extracellular fluid variations and cardiac disease status early, both important factors associated with hard outcomes.

Adverse Childhood Experiences and the Structure of Personality in Patients with Takotsubo Syndrome Versus Myocardial Infarction

Context and Aims: Psychosocial risk factors are known to result in either takotsubo syndrome (TTS) or myocardial infarction (MI). In this article, the results of a cross-sectional study are presented within the framework of “progressive somatization” by comparing the psychosocial traits of TTS and MI patients. Design/Subjects and Methods: 136 patients were administered a battery of questionnaires comprising the Childhood Trauma Questionnaire (CTQ), the Toronto Alexithymia Scale (TAS-20), the Experiences in Close Relationships-Revised Questionnaire, and the Operationalised Psychodynamic Diagnosis Structural Questionnaire (OPD-SQ). Life events prior to the onset of cardiac disease were recorded. Statistical Analysis: Descriptive statistics data were expressed in absolute numbers, percent, and mean and standard deviation. To identify differences between groups, T-tests for independent samples, Chi-square-tests and Mann-Whitney-Tests were used. Pearson correlations were computed to assess the relationship between the patient samples as well as between the patient samples and norms. Results: Few differences were found between TTS and MI patients, with both groups reporting moderate-to-severe “emotional neglect” in their childhood (CTQ). Compared to the norm group, TTS and MI patients showed higher values of “alexithymia” (TAS-20), and MI patients reported higher “attachment avoidance”. There are more “structural limitations of the personality” in TTS and MI patients than in a psychosomatic sample (OPD-SQ). Conclusions: TTS as well as MI patients suffer from “adverse childhood experiences” and “structural limitations of personality.” The results sustain the psychosomatic theory of progressive somatization that leads to severe bodily diseases. Patients might benefit from a specific psychotherapeutical support.

Myocardial overexpression of ANKRD1 causes sinus venosus defects and progressive diastolic dysfunction

Increased Ankyrin Repeat Domain 1 (ANKRD1) levels linked to gain of function mutations have been associated to total anomalous pulmonary venous return and adult cardiomyopathy occurrence in humans. The link between increased ANKRD1 level and cardiac structural and functional disease is not understood. To get insight into this problem, we have generated a gain of function ANKRD1 mouse model by overexpressing ANKRD1 in the myocardium. Ankrd1 is expressed non-homogeneously in the embryonic myocardium, with a dynamic nucleo-sarcomeric localization in developing cardiomyocytes. ANKRD1 transgenic mice present sinus venosus defect, which originates during development by impaired remodelling of early embryonic heart. Adult transgenic hearts develop diastolic dysfunction with preserved ejection fraction, which progressively evolves into heart failure, as shown histologically and haemodynamically. Transgenic cardiomyocyte structure, sarcomeric assembly, and stability are progressively impaired from embryonic to adult life. Postnatal transgenic myofibrils also present characteristic functional alterations: impaired compliance at neonatal stage and impaired lusitropism in adult hearts. Altogether, our combined analyses suggest that impaired embryonic remodelling and adult heart dysfunction in ANKRD1 transgenic mice present a common ground of initial cardiomyocyte defects, which are exacerbated postnatally. Molecular analysis showed transient activation of GATA4-Nkx2.5 transcription in early transgenic embryos and subsequent dynamic transcriptional modulation within titin gene. ANKRD1 is a fine mediator of cardiomyocyte response to haemodynamic load in the developing and adult heart. Increased ANKRD1 levels are sufficient to initiate an altered cellular phenotype, which is progressively exacerbated into a pathological organ response by the high ventricular workload during postnatal life. Our study defines for the first time a unifying picture for ANKRD1 role in heart development and disease and provides the first mechanistic link between ANKRD1 overexpression and cardiac disease onset.

Abstract 252: Activated Fibroblast-specific Deletion of RhoA Reduces Cardiac Fibrosis Through Regulation of the Non-canonical p38-MAPK Signaling Pathway

Objective: Heart failure is a progressive disease characterized by cardiomyocyte (CM) loss, interstitial fibrosis, loss of ventricular compliance and chamber remodeling. Role of cardiac fibroblasts is implicated in the process, but specific molecular mechanisms regulating their function remain unclear. Previously, we showed that in mice, in response to stress, CM-specific deletion of RhoA, a Ras-related small G protein, accelerated cardiac dilation, with significant loss of contractile function, but it also significantly reduced cardiac fibrosis. Therefore, here, we focused on understanding the role of RhoA specifically in myofibroblast transformation and the fibrotic response. Results: We generated mice with activated fibroblast-specific deletion of RhoA using a tamoxifen (TMX) inducible periostin-cre promoter (RhoAfl/fl::PSTN Cre/+). 10-wk-old male RhoAfl/fl::PSTN Cre/+ or control mice were treated with angiotensin-phenylephrine (AngPE) or saline for 4 wk using osmotic minipumps and fed either with TMX or regular diet. Following TMX-AngPE treatment, the RhoAfl/fl::PSTN Cre/+ mice showed significantly decreased cardiac fibrosis, as compared to controls (0.9% vs. 3.2%, respectively). Moreover, while overall cardiac function following AngPE treatment was similar at 4 wk in all groups, hearts from the TMX-RhoAfl/fl::PSTN Cre/+ mice had significantly reduced septal thickness, as compared to controls. Expression of fetal genes, ANF, BNP, and β-MHC, as well as markers of fibrosis, including α-SMA and CTGF, were similarly induced in control and TMX-RhoAfl/fl::PSTN Cre/+ mice. However, TMX-RhoAfl/fl::PSTN Cre/+ mice had reduced expression of TGF-β1, thrombospondin-5 and Col1a2. Finally, RhoA deletion in activated fibroblasts did not affect the canonical TGFβ signaling pathway, as expected; instead, we found TMX-RhoAfl/fl::PSTN Cre/+ hearts had reduced non-canonical p38-MAPK signaling, suggestive of cellular-specific effects of RhoA regulation in the onset of cardiac disease and fibrosis. Conclusions: These data confirm the primacy of the RhoA pathway in the fibrotic response in vivo and identify potential novel downstream targets and possible therapeutic strategies for treatment of cardiac fibrosis and heart failure.

THE PROGNOSTIC IMPACT OF METABOLIC SYNDROME IN PATIENTS WITH TYPE 2 DIABETES

Objective: Metabolic syndrome (Met S) is involved in the development of cardiovascular disease by promoting arteriosclerosis. In recent years, it is reported that obesity is related to an increase in the risk of malignant tumors. We examined the prognostic impact of metabolic syndrome in patients with type 2 diabetes by 8-year follow-up. Design and method: Seventy-one patients with type 2 diabetes without antihypertensive drugs (47 men, age 50 (mean) years-old) were recruited. Patients with a history of cardiac and cerebrovascular disease, and with chronic kidney disease were excluded. In the echocardiogram, left ventricular inner diameter was measured and left ventricular mass and function (FS and A/E) were calculated. Visceral fat area and subcutaneous fat area were measured using a CT scan of the navel region, and adipocytokines and fasting IRI and 24 hour urine CPR were measured. The end point was an onset of cardiac disease, cerebrovascular disease, malignant tumors event. Results: Fourty-four patients were Met S. The average follow-up period was 6.6 years and the follow-up rate was 94%. In the Met S group, 12 patients (29%) had end point events, 6 cardiac disease, 3 cerebrovascular disease, 3 malignant tumors. In the non-Met S group, 2 patients (7%) had the events, cardiovascular disease and malignant tumors. In Kaplan-Meier survival analysis, the incidence rates in the Met S group significantly increased compared to the non Met S group (p < 0.05). When cardiac disease and cerebrovascular disease were combined, the incidence rate was higher in the Met S group than the non Met S group (p < 0.05). In Cox regression analysis, the presence of Met S, decreased eGFR were independent risk factors of the onset of the total event (p < 0.05). And decreased eGFR and decreased E / A were independent risk factors of the onset of cardiac and cerebrovascular disease (p < 0.05). Conclusions: It was suggested that Met S induced worsening of prognosis in patients with Type 2 diabetes mellitus compared to those without Met S in total events including malignant tumors as well as arteriosclerotic diseases.

Electrocardiographic abnormalities in Chagas disease in the general population: A systematic review and meta-analysis.

BackgroundChagas disease (CD) is a major public health concern in Latin America and a potentially serious emerging threat in non-endemic countries. Although the association between CD and cardiac abnormalities is widely reported, study design diversity, sample size and quality challenge the information, calling for its update and synthesis, which would be very useful and relevant for physicians in non-endemic countries where health care implications of CD are real and neglected. We performed to systematically review and meta-analyze population-based studies that compared prevalence of overall and specific ECG abnormalities between CD and non-CD participants in the general population.MethodsSix databases (EMBASE, Ovid Medline, Web of Science, Cochrane Central, Google Scholar and Lilacs) were searched systematically. Observational studies were included. Odds ratios (OR) were computed using random-effects model.ResultsForty-nine studies were selected, including 34,023(12,276 CD and 21,747 non-CD). Prevalence of overall ECG abnormalities was higher in participants with CD (40.1%; 95%CIs=39.2-41.0) compared to non-CD (24.1%; 95%CIs=23.5-24.7) (OR=2.78; 95%CIs=2.37-3.26). Among specific ECG abnormalities, prevalence of complete right bundle branch block (RBBB) (OR=4.60; 95%CIs=2.97-7.11), left anterior fascicular block (LAFB) (OR=1.60; 95%CIs=1.21-2.13), combination of complete RBBB/LAFB (OR=3.34; 95%CIs=1.76-6.35), first-degree atrioventricular block (A-V B) (OR=1.71; 95%CIs=1.25-2.33), atrial fibrillation (AF) or flutter (OR=2.11; 95%CIs=1.40-3.19) and ventricular extrasystoles (VE) (OR=1.62; 95%CIs=1.14-2.30) was higher in CD compared to non-CD participants.ConclusionsThis systematic review and meta-analysis provides an update and synthesis in this field. This research of observational studies indicates a significant excess in prevalence of ECG abnormalities (40.1%) related to T. cruzi infection in the general population from Chagas endemic regions, being the most common ventricular (RBBB and LAFB), and A-V B (first-degree) node conduction abnormalities as well as arrhythmias (AF or flutter and VE). Also, prevalence of ECG alterations in children was similar to that in adults and suggests earlier onset of cardiac disease.

The prevalence and prognostic importance of possible familial hypercholesterolemia in patients with myocardial infarction

Familial hypercholesterolemia (FH) is a common genetic disorder causing accelerated atherosclerosis and premature cardiovascular disease. The aim of this study was to examine the prevalence and prognostic significance of possible FH in patients with myocardial infarction (MI). By individual-level linkage of data from the Eastern Danish Heart Registry and national administrative registries, a study population of patients referred for coronary angiography due to MI was selected. The study population was divided into "unlikely FH" and "possible FH" based on the Dutch Lipid Clinic Network criteria, which included a plasma low-density lipoprotein cholesterol (LDL-C) and age for onset of cardiac disease. A score of ≥3 points was used as the cutpoint between the 2 groups. Among the study population of 13,174 MI patients, 1,281 (9.7%) had possible FH. These patients were younger (59.1 vs 65.7 years, P ≤ .0001), had similar levels of comorbidities, and were treated more aggressively with cholesterol-lowering drugs compared with patients with unlikely FH. During a median of 3.3 years of follow-up, the unadjusted and adjusted event rates of recurrent MI were higher in patients with possible FH compared with unlikely FH (16% vs 11%, adjusted hazard ratio 1.28, 95% CI 1.09-1.51, P = .003.). Differences in adjusted all-cause mortality were not statistically significant (17% vs 23%, adjusted hazard ratio 0.89 [0.74-1.04], P = .1). We found that MI patients with possible FH have higher risk of recurrent MI but similar risk of mortality compared with unlikely FH patients. Further studies on secondary prevention are warranted.

Psychiatric Disorders In Takotsubo Cardiomyopathy Compared With Acute Coronary Syndrome Patients

Introduction: Depression and anxiety represent a common pathway for patients presenting with Takotsubo Cardiomyopathy (TTC) and Acute Coronary Syndrome (ACS) although differences in prevalence and their potential relation to cardiac disease onset remain to be described. Method and Results: 41 consecutive female patients with diagnosis of TTC were prospectively enrolled and compared with 82 consecutive age/sex matched patients with ACS as control group in a 1:2 fashion. Prevalence of psychological disorder was significantly higher in TTC patients compared with ACS (49% vs 26% p=0.01). In the subgroup with psychological disease, patients with TTC were more often anxious, while patients with ACS were more often affected by depression (80% vs 38% and 15% vs 48% respectively, p=0.02). At multiple regres-sion analysis TTC was an independent predictor of psychiatric disorders (HR 1.28 CI 1.1-1.5, p<0.01). Conclusion: In a cohort of elderly women with TTC, the prevalence of psychological disease is higher and with oppo-site clinical features (anxious vs depressed) compared with a matched ACS cohort.

Close proximity to busy roads increases the prevalence and onset of cardiac disease – Results from RHINE Tartu

ObjectivesTo analyze whether living close to a busy road would increase the risk of having cardiac disease and hypertension. Study designLongitudinal cross-sectional study. MethodsWe used cross-sectional longitudinal questionnaire data from the RHINE study for Tartu in 2000/2001 and 2011/2012. Home addresses of the respondents were geocoded and traffic data obtained from annually conducted traffic counts in Tartu. Relationships between proximity to a busy road and self-reported cardiac disease and hypertension were analyzed with multiple logistic regression. ResultsIn terms of total traffic (≥10,000 vehicles per day) within a 150-m zone of a busy road, the odds ratio (OR) for prevalence of cardiac disease was significant in 2000/2001 (1.91, 95% CI 1.15–3.16) and 2011/2012 (1.58, 95% CI 1.01–2.47). Prevalence of hypertension was significant only in 2011/2012 (1.61, 95% CI 1.08–2.39). In terms of heavy duty vehicle traffic (≥500 vehicles per day) within a 150-m zone in 2000/2001, the OR was 1.52 (95% CI 1.04–2.24) and 1.49 (95% CI 1.02–2.17) respectively for the prevalence of cardiac disease and hypertension. In 2011/2012 no significant relationship between heavy duty vehicle traffic and cardiac disease or hypertension was found. We also saw a significant relationship between total traffic and the onset of cardiac disease (OR = 2.04, 95% CI 1.07–3.87). ConclusionsThis study showed that living closer than 150 m to a busy road can increase the odds of having cardiac disease and hypertension, which should be taken into account in city planning.

Titin mutations: the fall of Goliath.

Titin (TTN), the largest protein in the human body, forms powerful elastic filaments along the sarcomere of cardiomyocytes. This multifunctional protein is involved in numerous cellular processes, including sarcomeric assembly, stabilization and mechanosensing. Along physiological sarcomere lengths, TTN is also the most important determinant of the passive tension of cardiac muscle. However, as the giant Goliath was brought down by David's slingshot, so single-base-pair mutations in the gene encoding TTN (TTN) can ultimately impair to some degree a normal cardiac function. Since the first report on the involvement of TTN mutations in the development of hypertrophic cardiomyopathy, in 1999, dozens of other mutations have been described and associated with the onset of cardiac disease. In this review, we aim to explore some of the mechanisms underlying the functions of TTN, as well as the pathophysiological consequences arising from the expression of abnormal TTN isoforms resulting from mutations located along TTN.

Prevention and reversal of severe mitochondrial cardiomyopathy by gene therapy in a mouse model of Friedreich's ataxia

Cardiac failure is the most common cause of mortality in Friedreich's ataxia (FRDA), a mitochondrial disease characterized by neurodegeneration, hypertrophic cardiomyopathy and diabetes. FRDA is caused by reduced levels of frataxin (FXN), an essential mitochondrial protein involved in the biosynthesis of iron-sulfur (Fe-S) clusters. Impaired mitochondrial oxidative phosphorylation, bioenergetics imbalance, deficit of Fe-S cluster enzymes and mitochondrial iron overload occur in the myocardium of individuals with FRDA. No treatment exists as yet for FRDA cardiomyopathy. A conditional mouse model with complete frataxin deletion in cardiac and skeletal muscle (Mck-Cre-Fxn(L3/L-) mice) recapitulates most features of FRDA cardiomyopathy, albeit with a more rapid and severe course. Here we show that adeno-associated virus rh10 vector expressing human FXN injected intravenously in these mice fully prevented the onset of cardiac disease. Moreover, later administration of the frataxin-expressing vector, after the onset of heart failure, was able to completely reverse the cardiomyopathy of these mice at the functional, cellular and molecular levels within a few days. Our results demonstrate that cardiomyocytes with severe energy failure and ultrastructure disorganization can be rapidly rescued and remodeled by gene therapy and establish the preclinical proof of concept for the potential of gene therapy in treating FRDA cardiomyopathy.

An innovative numerical approach to resolve the pulse wave velocity in a healthy thoracic aorta model

Aortic dissection and atherosclerosis are highly fatal diseases. The development of both diseases is closely associated with highly complex haemodynamics. Thus, in predicting the onset of cardiac disease, it is desirable to obtain a detailed understanding of the flowfield characteristics in the human cardiovascular circulatory system. Accordingly, in this study, a numerical model of a normal human thoracic aorta is constructed using the geometry information obtained from a phase-contrast magnetic resonance imaging (PC-MRI) technique. The interaction between the blood flow and the vessel wall dynamics is then investigated using a coupled fluid–structure interaction (FSI) analysis. The simulations focus specifically on the flowfield characteristics and pulse wave velocity (PWV) of the blood flow. Instead of using a conventional PC-MRI method to measure PWV, we present an innovative application of using the FSI approach to numerically resolve PWV for the assessment of wall compliance in a thoracic aorta model. The estimated PWV for a normal thoracic aorta agrees well with the results obtained via PC-MRI measurement. In addition, simulations which consider the FSI effect yield a lower predicted value of the wall shear stress at certain locations in the cardiac cycle than models which assume a rigid vessel wall. Consequently, the model provides a suitable basis for the future development of more sophisticated methods capable of performing the computer-aided analysis of aortic blood flows.