Stress and Heart in Remodeling Process: Multiple Stressors at the Same Time Kill.

Myocardial remodeling is developed by increased stress in acute or chronic pathophysiologies. Stressed heart morphology (SHM) is a new description representing basal septal hypertrophy (BSH) caused by emotional stress and chronic stress due to increased afterload in hypertension. Acute stress cardiomyopathy (ASC) and hypertension could be together in clinical practice. Therefore, there are some geometric and functional aspects regarding this specific location, septal base under acute and chronic stress stimuli. The findings by our and the other research groups support that hypertension-mediated myocardial involvement could be pre-existed in ASC cases. Beyond a frequently seen predominant base, hyperkinetic tissue response is detected in both hypertension and ASC. Furthermore, hypertension is the responsible factor in recurrent ASC. The most supportive prospective finding is BSH in which a hypercontractile base takes a longer time to exist morphologically than an acutely developed syndrome under both physiologic exercise and pressure overload by transaortic binding in small animals using microimaging. However, cardiac decompensation with apical ballooning could mask the possible underlying hypertensive disease. In fact, enough time for the assessment of previous hypertension history or segmental analysis could not be provided in an emergency unit, since ASC is accepted as an acute coronary syndrome during an acute episode. Additional supportive findings for SHM are increased stress scores in hypertensive BSH and the existence of similar tissue aspects in excessive sympathetic overdrive like pheochromocytoma which could result in both hypertensive disease and ASC. Exercise hypertension as the typical form of blood pressure variability is the sum of physiologic exercise and pathologic increased blood pressure and results in increased mortality. Hypertension is not rare in patients with a high stress score and leads to repetitive attacks in ASC supporting the important role of an emotional component as well as the potential danger due to multiple stressors at the same time. In the current review, the impact of multiple stressors on segmental or global myocardial remodeling and the hazardous potential of multiple stressors at the same time are discussed. As a result, incidentally determined segmental remodeling could be recalled in patients with multiple stressors and contribute to the early and combined management of both hypertension and chronic stress in the prevention of global remodeling and heart failure.

Role of Imaging in the Diagnosis, Evaluation, and Management of Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is increasingly recognized and may benefit from the recent approval of new, targeted medical therapy. Successful management of HCM is dependent on early and accurate diagnosis. The lack of a definitive diagnostic test, the wide variation in phenotype and the commonness of phenocopy conditions, and the presence of normal or hyperdynamic left ventricular function in most patients makes HCM a condition that is highly dependent on imaging for all aspects of management including, diagnosis, classification, predicting risk of complications, detecting complications, identifying risk for ventricular arrhythmias, evaluating choice of therapy and monitoring therapy, intraprocedural guidance, and screening family members. Although echocardiographic imaging remains the mainstay in the diagnosis and subsequent management of HCM, this disease clearly requires multimethod imaging for various aspects of optimal patient care. Advances in echocardiography hardware and techniques, development and refinement of imaging with computed tomography, magnetic resonance, and nuclear scanning, and the emergence of very focused assessments such as diastology and fibrosis imaging have all advanced the diagnosis and management of HCM. In this review, we discuss the relative utility and evidence support for these imaging approaches to contribute to improve patient outcomes.

Differences in Health-Related Quality of Life among Patients with Heart Failure.

Heart failure (HF) is characterized by a progressive clinical course marked by frequent exacerbations and repeated hospitalizations, leading to considerably high morbidity and mortality rates. Patients with HF present with a constellation of bothersome symptoms, which range from physical to psychological and mental manifestations. With the transition to more advanced HF stages, symptoms become increasingly more debilitating, interfere with activities of daily living and disrupt multiple domains of life, including physical functioning, psychological status, emotional state, cognitive function, intimate relationships, lifestyle status, usual role activities, social contact and support. By inflicting profuse limitations in numerous aspects of life, HF exerts a profoundly negative impact on health-related quality of life (HRQOL). It is therefore not surprising that patients with HF display lower levels of HRQOL compared not only to the general healthy population but also to patients suffering from other chronic diseases. On top of this, poor HRQOL in patients with HF becomes an even greater concern considering that it has been associated with unfavorable long-term outcomes and poor prognosis. Nevertheless, HRQOL may differ significantly among patients with HF. Indeed, it has consistently been reported that women with HF display poorer HRQOL compared to men, while younger patients with HF tend to exhibit lower levels of HRQOL than their older counterparts. Moreover, patients presenting with higher New York Heart Association (NYHA) functional class (III-IV) have significantly more impaired HRQOL than those in a better NYHA class (I-II). Furthermore, most studies report worse levels of HRQOL in patients suffering from HF with preserved ejection fraction (HFpEF) compared to patients with HF with reduced ejection fraction (HFrEF) or HF with mildly reduced ejection fraction (HFmrEF). Last, but not least, differences in HRQOL have been noted depending on geographic location, with lower HRQOL levels having been recorded in Africa and Eastern Europe and higher in Western Europe in a recent large global study. Based on the observed disparities that have been invariably reported in the literature, this review article aims to provide insight into the underlying differences in HRQOL among patients with HF. Through an overview of currently existing evidence, fundamental differences in HRQOL among patients with HF are analyzed based on sex, age, NYHA functional class, ejection fraction and geographic location or ethnicity.

Left Atrial Strain Derived From Cardiac Magnetic Resonance Imaging Can Predict Outcomes of Patients With Acute Myocarditis.

OBJECTIVE: There is increasing recognition that left atrial (LA) strain can be a prognostic marker of various cardiac diseases. However, its prognostic value in acute myocarditis remains unclear. Therefore, this study aimed to evaluate whether cardiovascular magnetic resonance (CMR)-derived parameters of LA strain can predict outcomes in patients with acute myocarditis. MATERIALS AND METHODS: We retrospectively analyzed the data of 47 consecutive patients (44.2 ± 18.3 years; 29 males) with acute myocarditis who underwent CMR in 13.5 ± 9.7 days (range, 0-31 days) of symptom onset. Various parameters, including feature-tracked CMR-derived LA strain, were measured using CMR. The composite endpoints included cardiac death, heart transplantation, implantable cardioverter-defibrillator or pacemaker implantation, rehospitalization following a cardiac event, atrial fibrillation, or embolic stroke. The Cox regression analysis was performed to identify associations between the variables derived from CMR and the composite endpoints. RESULTS: After a median follow-up of 37 months, 20 of the 47 (42.6%) patients experienced the composite events. In the multivariable Cox regression analysis, LA reservoir and conduit strains were independent predictors of the composite endpoints, with an adjusted hazard ratio per 1% increase of 0.90 (95% confidence interval [CI], 0.84-0.96; P = 0.002) and 0.91 (95% CI, 0.84-0.98; P = 0.013), respectively. CONCLUSION: LA reservoir and conduit strains derived from CMR are independent predictors of adverse clinical outcomes in patients with acute myocarditis.

Ultimate phases of hypertensive heart disease and stressed heart morphology by conventional and novel cardiac imaging.

Early recognition of hypertensive heart disease is needed to prevent macrovascular and microvascular damage. Hypertension (HTN) is a risk factor for coronary artery disease, and plays a prominent role in the development of adverse left ventricular (LV) remodeling and heart failure. Here, we review new knowledge on effects of HTN on cardiac geometry and function, obtained from multimodality cardiac imaging, including echocardiography, positron emission tomography and magnetic resonance imaging. Early recognition of changes in LV geometry and function induced by HTN could identify patients at risk for end-organ damage, who could be targeted for close monitoring and intensive therapy. Basal septal hypertrophy as the early imaging biomarker at the adaptive phase may be a specific aspect not only in hypertensive heart but stress-related conditions and called stressed heart morphology.

Basal Septal Hypertrophy as the Early Imaging Biomarker for Adaptive Phase of Remodeling Prior to Heart Failure.

Hypertension plays a dominant role in the development of left ventricular (LV) remodeling and heart failure, in addition to being the main risk factor for coronary artery disease. In this review, we focus on the focal geometric and functional tissue aspects of the LV septal base, since basal septal hypertrophy (BSH), as the early imaging biomarker of LV remodeling due to hypertensive heart disease, is detected in cross-sectional clinic studies. In addition, the validation of BSH by animal studies using third generation microimaging and relevant clinical observations are also discussed in the report. Finally, an evaluation of both human and animal quantitative imaging studies and the importance of combined cardiac imaging methods and stress-induction in the separation of adaptive and maladaptive phases of the LV remodeling are pointed out. As a result, BSH, as the early imaging biomarker and quantitative follow-up of functional analysis in hypertension, could possibly contribute to early treatment in a timely fashion in the prevention of hypertensive disease progression to heart failure. A variety of stress stimuli in etiopathogenesis and the difficulty of diagnosing pure hemodynamic overload mediated BSH lead to an absence of the certain prevalence of this particular finding in the population.

A variable resolution approach for improved acquisition of hyperpolarized 13 C metabolic MRI.

PURPOSE: To ameliorate tradeoffs between a fixed spatial resolution and signal-to-noise ratio (SNR) for hyperpolarized 13 C MRI. METHODS: In MRI, SNR is proportional to voxel volume but retrospective downsampling or voxel averaging only improves SNR by the square root of voxel size. This can be exploited with a metabolite-selective imaging approach that independently encodes each compound, yielding high-resolution images for the injected substrate and coarser resolution images for downstream metabolites, while maintaining adequate SNR for each. To assess the efficacy of this approach, hyperpolarized [1-13 C]pyruvate data were acquired in healthy Sprague-Dawley rats (n = 4) and in two healthy human subjects. RESULTS: Compared with a constant resolution acquisition, variable-resolution data sets showed improved detectability of metabolites in pre-clinical renal studies with a 3.5-fold, 8.7-fold, and 6.0-fold increase in SNR for lactate, alanine, and bicarbonate data, respectively. Variable-resolution data sets from healthy human subjects showed cardiac structure and neuro-vasculature in the higher resolution pyruvate images (6.0 × 6.0 mm2 for cardiac and 7.5 × 7.5 mm2 for brain) that would otherwise be missed due to partial-volume effects and illustrates the level of detail that can be achieved with hyperpolarized substrates in a clinical setting. CONCLUSION: We developed a variable-resolution strategy for hyperpolarized 13 C MRI using metabolite-selective imaging and demonstrated that it mitigates tradeoffs between a fixed spatial resolution and SNR for hyperpolarized substrates, providing both high resolution pyruvate and coarse resolution metabolite data sets in a single exam. This technique shows promise to improve future studies by maximizing metabolite SNR while minimizing partial-volume effects from the injected substrate.

Identifying Ventricular Arrhythmias and Their Predictors by Applying Machine Learning Methods to Electronic Health Records in Patients With Hypertrophic Cardiomyopathy (HCM-VAr-Risk Model).

Clinical risk stratification for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HC) employs rules derived from American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines or the HCM Risk-SCD model (C-index ∼0.69), which utilize a few clinical variables. We assessed whether data-driven machine learning methods that consider a wider range of variables can effectively identify HC patients with ventricular arrhythmias (VAr) that lead to SCD. We scanned the electronic health records of 711 HC patients for sustained ventricular tachycardia or ventricular fibrillation. Patients with ventricular tachycardia or ventricular fibrillation (n = 61) were tagged as VAr cases and the remaining (n = 650) as non-VAr. The 2-sample ttest and information gain criterion were used to identify the most informative clinical variables that distinguish VAr from non-VAr; patient records were reduced to include only these variables. Data imbalance stemming from low number of VAr cases was addressed by applying a combination of over- and undersampling strategies. We trained and tested multiple classifiers under this sampling approach, showing effective classification. We evaluated 93 clinical variables, of which 22 proved predictive of VAr. The ensemble of logistic regression and naïve Bayes classifiers, trained based on these 22 variables and corrected for data imbalance, was most effective in separating VAr from non-VAr cases (sensitivity = 0.73, specificity = 0.76, C-index = 0.83). Our method (HCM-VAr-Risk Model) identified 12 new predictors of VAr, in addition to 10 established SCD predictors. In conclusion, this is the first application of machine learning for identifying HC patients with VAr, using clinical attributes. Our model demonstrates good performance (C-index) compared with currently employed SCD prediction algorithms, while addressing imbalance inherent in clinical data.

Plasma homocysteine levels associated with a corrected QT interval.

BACKGROUND: Little is known about the relationship between homocysteine (Hcy) levels and the QT interval. We examined the association of different Hcy levels with corrected QT (QTc) intervals in a general population. METHODS: Plasma levels of Hcy were assessed in a population-based study of 7002 participants 35 years of age and older from 2012 to 2013. Twelve-lead ECGs were performed on all participants and analyzed automatically. RESULTS: The distribution of Hcy levels was determined for an entire population after the data were grouped into quartiles (Q1: <=11.1umol/L; Q2: 11.1-13.8umol/L; Q3: 13.8-18.2 umol/L; Q4 > 18.2 umol/L). The mean value of the QTc interval in each quartile was 433.2 ± 23.8 ms, 430.0 ± 24.6 ms, 429.2 ± 24.5 ms and 430.6 ± 25.7 ms. Multiple logistic regression analyses showed that, compared with the second quartile, and after fully adjusting for potential confounding factors, the odds for QTc > 440 ms in the first and fourth quartile increased (P < 0.05), (OR: 1.23, 95% CI: 1.05-1.43 for Q1; OR: 1.40, 95% CI: 1.19-1.65 for Q4). CONCLUSIONS: QTc interval was associated with the Hcy level in this general population.

Diagnosed but Not Undiagnosed Diabetes Is Associated with Depression in Rural Areas.

Background: There is a lack of study on the relation between undiagnosed diabetes and depression in the general population. Methods: A total of 11,531 adults were examined using a multistage cluster sampling method to select a representative sample of individuals who were at least 35 years old. Subjects were classified into three groups: no diabetes (ND), diagnosed diabetes (DD), and undiagnosed diabetes (UD). The participants were surveyed with the Patient Health Questionnaire-9 (PHQ-9). Results: Of all the 11,531 participants, the prevalence of depression was higher in the DD group than in the other two groups. Multi variable logistic regression analyses show that the DD group had significantly higher odds for depression compared with the ND group (p < 0.01), while the UD group showed no significant differences compared to the ND group. Subgroup analyses show that diagnosed diabetes in subjects with a lower educational level, compared with subjects with an educational level of high school or above, had higher odds for a PHQ-9 score ≥5 (p < 0.01). Conclusion: In this general population, diagnosed but not undiagnosed diabetes was significantly associated with depression. Much higher odds for depression were found among diagnosed diabetic individuals with a lower level of education.

Metabolism rather than obesity is associated with ischemic stroke: a cross-sectional study in rural Northeastern China.

Little is known about stroke with different obesity phenotype as determined using the Adult Treatment Panel-III criteria with metabolic health or not. This study aimed to investigate the effects of metabolically healthy and unhealthy obesity on ischemic stroke in a general population. A total of 11,150 adults were examined using a multi-stage cluster sampling method to select a representative sample of individuals 35 years or older. Ischemic stroke was defined as history of a cerebrovascular event, as documented by doctors via either cranial CT or MR scan within the past 2 years. All subjects were categorized as having metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO) or metabolically unhealthy obesity (MUO) using the Adult Treatment Panel-III criteria. Stratified analysis were done based on different body mass index group. For the total population, multiple regression analyses revealed that individuals with MUNO and MUO were more likely to experience ischemic stroke compared with those with MHNO (OR 2.136, 95 % CI 1.677-2.720; OR 2.712, 95 % CI 1.798-4.092; all p < 0.001). The OR for ischemic stroke did not significantly differ between MHO and MHNO. Stratification based on different BMI group showed that, compared with people who were normal weight without Mes, participants who were in Mes with overweight or obesity had significantly higher OR for ischemic stroke(both p < 0.05); participants who were not in Mes with overweight or obesity did not showed OR significantly higher. Ischemic stroke is likely associated with poor metabolic health rather than with obesity itself.

The Relation of Moderate Alcohol Consumption to Hyperuricemia in a Rural General Population.

BACKGROUND: although alcohol abuse is known to increase serum uric acid, the relation between moderate drinking and uric acid have remained poorly understood. We performed this study to evaluate whether different alcohol consumption level has different effects on the risk of hyperuricemia based on a rural general population. METHOD: multi-stage cluster sampling method was used to select a representative sample of individuals aged 35 years or older. Participants were asked to provide information about their alcohol consumption. Data regarding the demographic and lifestyle characteristics and the blood biochemical indexes of these participants were collected by well-trained personnel. RESULTS: in total, 11,039 participants aged 35 years or older were included (4997 men and 6042 women). The prevalence of hyperuricemia in the different male alcohol consumption groups was 11.9% in non-drinkers, 12.6% in moderate drinkers, and 16.3% in heavy drinkers (p < 0.001). In females, the rates were 6.3% in non-drinkers, 8.1% in moderate drinkers, and 6.6% for heavy drinkers (p = 0.818). In males, multivariate logistic regression analyses shows heavy drinkers had an approximately 1.7-fold higher risk of hyperuricemia (OR: 1.657, 95% CI: 1.368 to 2.007, p < 0.001) than non-drinkers; moderate drinkers did not experience a significant increase in risk (OR: 1.232, 95% CI: 0.951 to 1.596, p = 0.114)). Multivariate logistic regression analyses of females showed that, compared with non-drinkers, neither moderate nor heavy drinkers had a significantly increased risk of hyperuricemia (OR: 1.565, 95% CI: 0.521 to 4.695, p = 0.425 for heavy drinkers; OR: 0.897, 95% CI: 0.117 to 6.855, p = 0.916 for moderate drinkers). CONCLUSIONS: heavy alcohol consumption increased the risk of hyperuricemia for males but not for females. Among both males and females, moderate alcohol consumption did not increase the risk of hyperuricemia.

Left ventricular wall thickness in patients with hypertrophic cardiomyopathy: a comparison between cardiac magnetic resonance imaging and echocardiography.

We assessed whether cardiac MRI (CMR) and echocardiography (echo) have significant differences measuring left ventricular (LV) wall thickness (WT) in hypertrophic cardiomyopathy (HCM) as performed in the clinical routine. Retrospectively identified, clinically diagnosed HCM patients with interventricular-septal (IVS) pattern hypertrophy who underwent CMR and echo within the same day were included. Left Ventricular WT was measured by CMR in two planes and compared to both echo and contrast echo (cecho). 72 subjects, mean age 50.7 ± 16.2 years, 68 % males. Interventricular septal WT by echo and CMR planes showed good to excellent correlation. However, measurements of the postero-lateral wall showed poor correlation. Bland-Altman plots showed greater maximal IVS WT by echo compared to CMR measurement [SAX = 1.7 mm (-5.8, 9.3); LVOT = 1.1 mm (-5.6, 7.8)]. Differences were smaller between cecho and CMR [SAX = 0.8 mm (-9.2, 10.8); LVOT = -0.2 mm (-10.0, 9.6)]. Severity of WT by quartiles showed greater differences between echo and SAX CMR WT compared to cecho. Echocardiography typically measures greater WT than CMR, with the largest differences in moderate to severe hypertrophy. Contrast echocardiography more closely approximates CMR measurements of WT. These findings have potential clinical implications for risk stratification of subjects with HCM.

Constitutive HIF-1α expression blunts the beneficial effects of cardiosphere-derived cell therapy in the heart by altering paracrine factor balance.

Hypoxia-inducible factor-1alpha (HIF-1α) expression promotes angiogenesis and can influence stem cell engraftment. We investigated the effect of stable over-expression of constitutively active HIF-1α on cardiosphere-derived cell (CDC) engraftment and left ventricular function. CDCs were transduced with a lentivirus expressing a constitutively active mutant of human HIF-1α (LVHIF-1α). Two million male rat CDCs were injected into the infarct following ligation of the mid-LAD in female syngeneic rats. Left ventricular ejection fraction (EF) and circumferential strain were measured by echocardiography at 1 and 4 weeks post-MI in the following groups: PBS group (n = 7), CELL group (n = 7), and CELL-HIF group (n = 7). HIF-1α, VEGF, endothelin-1 expression, and CDC engraftment were measured by quantitative PCR. At 30 days, EF was unchanged in the CELL-HIF group (p = NS), increased in the CELL group (p = 0.025), and decreased in the PBS group (p = 0.021), but engraftment was similar (2.4% ± 3.3% vs 1.7% ± 0.8%, p = NS). Mean circumferential strain of the infarcted region was unchanged in the CELL-HIF group, but improved in the CELL group (p = 0.02). Endothelin-1 and VEGF expression were higher in HIF-CDCs exposed to hypoxia, compared with non-transduced CDCs. HIF-1α expression in CDCs blunted the beneficial functional effects of CDC transplantation, suggesting that paracrine factor balance may play an important role in cardiac regeneration.