Hiccups And Heart Disease

Doctors and heart patents take note of this, abstract:

Hiccups, which are usually benign and self-limited, occasionally serve as markers of a serious underlying pathology. We present this case report to inform emergency physicians about the potential for hiccups to serve as the only presenting symptom of a myocardial infarction. The patient, a 68-year-old man with a history of diabetes mellitus, hypertension, and current tobacco use, was first seen in the emergency department after 4 days of intractable hiccups with no other complaints or symptoms. After ineffective hiccup treatment on the first visit with 2 mg Ativan and 25 intramuscular (i.m.) thorazine and a normal chest x-ray, he was discharged. Two days later, the patient returned to the emergency department with the same complaint of hiccups without any additional complaints or symptoms. An electrocardiogram displayed several abnormalities including Q waves in II, III, and aVF and T-wave inversions in aVL and V6. Troponin I was highly elevated at 4.302 ng/mL. In the catheterization laboratory, the patient exhibited severe stenosis of the left circumflex artery and obtuse marginal 1. Stents were placed in these sites, and the patient recovered uneventfully. This is the first case in which hiccups were the single presenting symptom of a myocardial infarction in the last 50 years. Although extremely common and usually benign, hiccups can occasionally be a sole symptom of serious underlying pathology, which in this case, was a non–ST-segment elevation myocardial infarction.

Resveratrol And VDR

Resveratrol is purported to have a number of health benefits; this paper explains one possible mechanism of action, abstract:

The 1,25-dihydroxyvitamin D3 (1,25D) hormone is derived from vitamin D generated in skin or obtained from the diet, and binds to and activates the vitamin D receptor (VDR) in target tissues including kidney, colon/small intestine, and bone/muscle. We tested resveratrol for its ability to modulate VDR signaling, using vitamin D responsive element (VDRE) and mammalian 2-hybrid (M2H) transcriptional system technology. Via VDRE-based assays in kidney, colon and myoblast cells, VDR-mediated transcription was activated by resveratrol, and a cooperative effect on transactivation was observed with resveratrol plus 1,25D. The M2H assay revealed a modest, resveratrol-induced dimerization of VDR with its retinoid X receptor (RXR) heteropartner. Cells treated with both resveratrol and 1,25D displayed synergistic stimulation of VDR-RXR heterodimerization, while resveratrol antagonized rexinoid-mediated RXR-RXR homodimerization. Increased transactivation in response to resveratrol was also observed with a subset of other nuclear receptors and their respective cognate responsive elements. Evaluation of wild-type versus a ligand-binding domain mutant VDR revealed that hormone-responsiveness to 1,25D was severely depressed, while the response to resveratrol was only moderately attenuated. Moreover, radiolabeled 1,25D-displacement assays demonstrated an increase in VDR-bound 1,25D in the presence of resveratrol. Thus, resveratrol may affect VDR and other nuclear receptors indirectly, likely via the ability of resveratrol to: (1) potentiate 1,25D binding to VDR; (2) activate RXR; and/or (3) stimulate SIRT1, an enzyme known to deacetylate nuclear receptors. The results of this study elucidate a possible pathway for crosstalk between two nutritionally derived lipids, vitamin D and resveratrol, both of which converge on VDR signaling.

Vitamin D and vitamin D signaling continuously proves to be extremely important for human health and disease prevention.

Diet And Cardiometabolic Deaths

From several years ago is a study the emphasizes what we should all hopefully already know - some foods increase the risk of death from cardiovascular events and other foods decrease that risk.  Here is the Results section from the Abstract; I am bold-fonting the important points for ease of reading:

RESULTS:In 2012, 702 308 cardiometabolic deaths occurred in US adults, including 506 100 from heart disease (371 266 coronary heart disease, 35 019 hypertensive heart disease, and 99 815 other cardiovascular disease), 128 294 from stroke (16 125 ischemic, 32 591 hemorrhagic, and 79 578 other), and 67 914 from type 2 diabetes. Of these, an estimated 318 656 (95% uncertainty interval [UI], 306 064-329 755; 45.4%) cardiometabolic deaths per year were associated with suboptimal intakes-48.6% (95% UI, 46.2%-50.9%) of cardiometabolic deaths in men and 41.8% (95% UI, 39.3%-44.2%) in women; 64.2% (95% UI, 60.6%-67.9%) at younger ages (25-34 years) and 35.7% (95% UI, 33.1%-38.1%) at older ages (≥75 years); 53.1% (95% UI, 51.6%-54.8%) among blacks, 50.0% (95% UI, 48.2%-51.8%) among Hispanics, and 42.8% (95% UI, 40.9%-44.5%) among whites; and 46.8% (95% UI, 44.9%-48.7%) among lower-, 45.7% (95% UI, 44.2%-47.4%) among medium-, and 39.1% (95% UI, 37.2%-41.2%) among higher-educated individuals. The largest numbers of estimated diet-related cardiometabolic deaths were related to high sodium (66 508 deaths in 2012; 9.5% of all cardiometabolic deaths), low nuts/seeds (59 374; 8.5%), high processed meats (57 766; 8.2%), low seafood omega-3 fats (54 626; 7.8%), low vegetables (53 410; 7.6%), low fruits (52 547; 7.5%), and high SSBs (51 694; 7.4%). Between 2002 and 2012, population-adjusted US cardiometabolic deaths per year decreased by 26.5%. The greatest decline was associated with insufficient polyunsaturated fats (-20.8% relative change [95% UI, -18.5% to -22.8%]), nuts/seeds (-18.0% [95% UI, -14.6% to -21.0%]), and excess SSBs (-14.5% [95% UI, -12.0% to -16.9%]). The greatest increase was associated with unprocessed red meats (+14.4% [95% UI, 9.1%-19.5%]).

Talk to your physician about adjusting your diet accordingly. SSBs = sugar-sweetened beverages.

Melanesians, Non-Western Diet, And Cardiovascular Disease Risk

Why do some non-Western populations have low rates of stroke and heart disease?  Here is a paper looking at one such population.  Abstract (containing one spelling correction):

OBJECTIVES:

To compare cardiovascular risk factor levels between non-westernized Melanesians, apparently free from stroke and ischaemic heart disease, and healthy Swedish populations, and to analyse, among adult Melanesians, relations with age, sex and smoking status.

DESIGN:

Cross-sectional survey.

SUBJECTS:

(i) Traditional horticulturalists in Kitava, Trobriand Islands, Papua New Guinea, uninfluenced by western diet. this study tested 151 males and 69 females aged 14-87 years with 76% and 80% smokers over 20 years. (ii) Healthy Swedish reference populations.

MAIN OUTCOME MEASURES:

Sitting systolic and diastolic blood pressure, weight, height, body mass index, circumferences of waist, pelvis and mid upper arm, triceps skinfold thickness, fasting serum total cholesterol, triglycerides, high-density lipoprotein cholesterol, estimated low-density lipoprotein cholesterol, apolipoprotein B, apolipoprotein A1 and apolipoprotein (a).

RESULTS:

Compared to Sweden, diastolic blood pressure, body mass index and triceps skinfold thickness were substantially lower in Kitava, where all subjects > or = 40 years were below Swedish medians. Among males > or = 20 and females > or = 60 years systolic blood pressure was lower in Kitavans. Fasting serum total cholesterol, low-density lipoprotein cholesterol and apolipoprotein B were 10-30% lower in Kitavan males > or = 40 and females > or = 60 years. Triglycerides were higher in Kitavans aged 20-39. High-density lipoprotein cholesterol did not differ while apolipoprotein A1 was lower in Kitavans. Apolipoprotein (a) tended to be lower in Kitavans, but the differences were small.

CONCLUSIONS:

Of the analysed variables, leanness and low diastolic blood pressure seem to offer the best explanations for the apparent absence of stroke and ischaemic heart disease in Kitava. The lower serum cholesterol may provide some additional benefit. Differences in dietary habits may explain the findings.

So, dietary differences leading to lean body structure, lower blood pressure, and lower cholesterol levels may explain the better stroke/heart disease profile in Melanesians vs. Swedes.  Of course, genetic differences, not mentioned in this abstract, between the two populations may influence this as well.  What I would like to see is a study comparing people within each population, each group having a different diet.  For example, do Melanesians with a Western diet have higher rates to stroke and heart disease?  What about Swedes on a healthier diet?

Saline Infusion For Postural Tachycardia Syndrome

Treatment for option for postural tachycardia syndrome described here, abstract:

BACKGROUND: The postural tachycardia syndrome (POTS) is a heterogeneous group of disorders that results in symptoms of orthostatic intolerance. Excess blood pooling has been observed to cause low effective circulating volume in the central vasculature. Consequently, acute volume loading with IV saline has emerged as a potential strategy for clinical intervention. We evaluated the impact of acute volume loading on both the signs and symptoms of patients suffering from POTS.

METHODS: Fifty-seven subjects screened from our population of POTS patients and assenting to participation were administered the two surveys by telephone. Subjects completed each survey twice, before, and after initiating IV hydration therapy. The Orthostatic Hypotension Questionnaire (OHQ) was used to assess change in clinical symptomatology, while the short form 36 health survey (SF-36) was employed to assess the impact of IV saline infusion on quality of life.
RESULTS: Fifty-seven patients were included in the analysis. The average number of medications trialed before referral for IV hydration was 3.6 ± 1.7 medications. Saline infusions occurred with mean frequency of 11.3 ± 8.5 days and at a mean volume of 1.5 ± 0.6 l per infusion. The mean change of the OHQ was 3.1 ± 0.3 (95% CI 2.6-3.7; P < 0.001), with significant improvement in all the composite scores. The mean change in the SF-36 form was 19.1 ± 2.7 (95% CI -24.6 to -13.6; P < 0.001).
CONCLUSIONS: Intermittent IV infusions of saline dramatically reduce symptoms and improve quality of life in patients suffering from POTS. Further work should explore its efficacy as a bridge study for patients of high symptomatic severity.

So, something simple such as saline infusion can have a significant positive impact on the symptoms of this disorder; this may be something patients afflicted with this syndrome should discuss with their physicians.

Aging And Heart Failure Links

The obvious aging-heart failure link has links to cell signaling; understanding these links can lead to novel therapies.  Abstract:

The molecular pathophysiology of heart failure, which is one of the leading causes of mortality, is not yet fully understood. Heart failure can be regarded as a systemic syndrome of aging-related phenotypes. Wnt/β-catenin signaling and the p53 pathway, both of which are key regulators of aging, have been demonstrated to play a critical role in the pathogenesis of heart failure. Circulating C1q was identified as a novel activator of Wnt/β-catenin signaling, promoting systemic aging-related phenotypes including sarcopenia and heart failure. On the other hand, p53 induces the apoptosis of cardiomyocytes in the failing heart. In these molecular mechanisms, the cross-talk between cardiomyocytes and non-cardiomyocytes (e,g,. endothelial cells, fibroblasts, smooth muscle cells, macrophages) deserves mentioning. In this review, we summarize recent advances in the understanding of the molecular pathophysiology underlying heart failure, focusing on Wnt/β-catenin signaling and the p53 pathway.

Sudden Cardiac Arrest In Sports

Sudden cardiac arrest when playing sports is rare.  However, keep in mind that particular individuals may be at higher risk, which is why you should consult with a physician before starting any sort of exercise program or sport; a possibility exists of a heart defect or other abnormality.  Abstract:

BACKGROUND:

The incidence of sudden cardiac arrest during participation in sports activities remains unknown. Preparticipation screening programs aimed at preventing sudden cardiac arrest during sports activities are thought to be able to identify at-risk athletes; however, the efficacy of these programs remains controversial. We sought to identify all sudden cardiac arrests that occurred during participation in sports activities within a specific region of Canada and to determine their causes.

METHODS:

In this retrospective study, we used the Rescu Epistry cardiac arrest database (which contains records of every cardiac arrest attended by paramedics in the network region) to identify all out-of-hospital cardiac arrests that occurred from 2009 through 2014 in persons 12 to 45 years of age during participation in a sport. Cases were adjudicated as sudden cardiac arrest (i.e., having a cardiac cause) or as an event resulting from a noncardiac cause, on the basis of records from multiple sources, including ambulance call reports, autopsy reports, in-hospital data, and records of direct interviews with patients or family members.

RESULTS:

Over the course of 18.5 million person-years of observation, 74 sudden cardiac arrests occurred during participation in a sport; of these, 16 occurred during competitive sports and 58 occurred during noncompetitive sports. The incidence of sudden cardiac arrest during competitive sports was 0.76 cases per 100,000 athlete-years, with 43.8% of the athletes surviving until they were discharged from the hospital. Among the competitive athletes, two deaths were attributed to hypertrophic cardiomyopathy and none to arrhythmogenic right ventricular cardiomyopathy. Three cases of sudden cardiac arrest that occurred during participation in competitive sports were determined to have been potentially identifiable if the athletes had undergone preparticipation screening.

CONCLUSIONS:

In our study involving persons who had out-of-hospital cardiac arrest, the incidence of sudden cardiac arrest during participation in competitive sports was 0.76 cases per 100,000 athlete-years. The occurrence of sudden cardiac arrest due to structural heart disease was uncommon during participation in competitive sports. (Funded by the National Heart, Lung, and Blood Institute and others.).

Inhibiting Hippo For Heart Repair

Altering cell signaling pathways, as discussed here with the Hippo pathway, holds promise to enhance the regenerative capacity of damaged tissues and organs, in this case, the heart, after heart failure. Abstract:

Mammalian organs vary widely in regenerative capacity. Poorly regenerative organs, such as the heart are particularly vulnerable to organ failure. Once established, heart failure commonly results in mortality. The Hippo pathway, a kinase cascade that prevents adult cardiomyocyte proliferation and regeneration, is upregulated in human heart failure. Here we show that deletion of the Hippo pathway component Salvador (Salv) in mouse hearts with established ischaemic heart failure after myocardial infarction induces a reparative genetic program with increased scar border vascularity, reduced fibrosis, and recovery of pumping function compared with controls. Using translating ribosomal affinity purification, we isolate cardiomyocyte-specific translating messenger RNA. Hippo-deficient cardiomyocytes have increased expression of proliferative genes and stress response genes, such as the mitochondrial quality control gene, Park2. Genetic studies indicate that Park2 is essential for heart repair, suggesting a requirement for mitochondrial quality control in regenerating myocardium. Gene therapy with a virus encoding Salv short hairpin RNA improves heart function when delivered at the time of infarct or after ischaemic heart failure following myocardial infarction was established. Our findings indicate that the failing heart has a previously unrecognized reparative capacity involving more than cardiomyocyte renewal.

Notch And The Heart

Notch signaling is required for proper heart function; abstract:

Background -Nutrients are transported through endothelial cells before being metabolized in muscle cells. However, little is known about the regulation of endothelial transport processes. Notch signaling is a critical regulator of metabolism and angiogenesis during development. Here, we studied how genetic and pharmacological manipulation of endothelial Notch signaling in adult mice affects endothelial fatty acid transport, cardiac angiogenesis, and heart function. Methods -Endothelial-specific Notch inhibition was achieved by conditional genetic inactivation of Rbp-jκ in adult mice to analyze fatty acid metabolism and heart function. Wild-type mice were treated with neutralizing antibodies against the Notch ligand Dll4. Fatty acid transport was studied in cultured endothelial cells and transgenic mice. Results -Treatment of wild-type mice with Dll4 neutralizing antibodies for eight weeks impaired fractional shortening and ejection fraction in the majority of mice. Inhibition of Notch signaling specifically in the endothelium of adult mice by genetic ablation of Rbp-jκ caused heart hypertrophy and failure. Impaired heart function was preceded by alterations in fatty acid metabolism and an increase in cardiac blood vessel density. Endothelial Notch signaling controlled the expression of endothelial lipase, Angptl4, CD36 and Fabp4, which are all needed for fatty acid transport across the vessel wall. In endothelial-specific Rbp-jκ-mutant mice lipase activity and transendothelial transport of long-chain fatty acids to muscle cells was impaired. In turn, there was accumulation of lipids in plasma and liver. The attenuated supply of cardiomyocytes with long-chain fatty acids was accompanied by higher glucose uptake, increased concentration of glycolysis intermediates and mTOR-S6K signaling. Treatment with the mTOR inhibitor rapamycin or displacing glucose as cardiac substrate by feeding a ketogenic diet prolonged survival of endothelial-specific Rbp-jκ-deficient mice. Conclusions -This study identifies Notch signaling as a novel regulator of fatty acid transport across the endothelium and as an essential repressor of angiogenesis in the adult heart. The data imply that the endothelium controls cardiomyocyte metabolism and function.

Against Fibrosis

By Nephron - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=8674830

Fibrosis, a disorder characterized by formation of excess connective fibrous tissue, is common in various disease states, including cardiovascular and kidney disease, negative affecting the function of these organs.  A new study suggests that inhibition of interleukin 11 signaling can repress fibrosis formation and can serve as a possible therapy for fibrotic disease.  Abstract:

Fibrosis is a final common pathology in cardiovascular disease1. In the heart, fibrosis causes mechanical and electrical dysfunction1,2 and in the kidney, it predicts the onset of renal failure3. Transforming growth factor β1 (TGFB1) is the principal pro-fibrotic factor4,5 but its inhibition is associated with side effects due to its pleiotropic roles6,7. We hypothesised that downstream effectors of TGFB1 in fibroblasts could be attractive therapeutic targets and lack upstream toxicities. Using integrated imaging-genomics analyses of primary human fibroblasts, we found that Interleukin 11 (IL11) upregulation is the dominant transcriptional response to TGFB1 exposure and required for its profibrotic effect. IL11 and its receptor (IL11RA) are expressed specifically in fibroblasts where they drive non-canonical, ERK-dependent autocrine signalling that is required for fibrogenic protein synthesis. In mice, fibroblast-specific Il11 transgene expression or Il11 injection causes heart and kidney fibrosis and organ failure whereas genetic deletion of Il11ra1 is protective against disease. Thus, inhibition of IL11 prevents fibroblast activation across organs and species in response to a range of important pro-fibrotic stimuli. These data reveal a central role of IL11 in fibrosis and we propose inhibition of IL11 as a new therapeutic strategy to treat fibrotic diseases.

Broken Heart Syndrome

By J. Heuser JHeuser - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=889151

Takotsubo cardiomyopathy or “broken heart syndrome” is a form of heart disease “precipitated by intense emotional stress.” It has previously been thought to be transient and reversible in nature, but a study has now shown sufferers exhibit long-term heart damage.  It is impossible to avoid intense emotional stress I life, but everyone must try and deal with it as best as they can, and if this disorder happens to them, they will seem to need long-term evaluation by a cardiac specialist. Abstract:

BACKGROUND: Takotsubo cardiomyopathy is an increasingly recognized acute heart failure syndrome precipitated by intense emotional stress. Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction, the long-term clinical and functional consequences of takotsubo cardiomyopathy are ill-defined. METHODS: In an observational case-control study, we recruited 37 patients with prior (>12-month) takotsubo cardiomyopathy, and 37 age-, sex-, and comorbidity-matched control subjects. Patients completed the Minnesota Living with Heart Failure Questionnaire. All participants underwent detailed clinical phenotypic characterization, including serum biomarker analysis, cardiopulmonary exercise testing, echocardiography, and cardiac magnetic resonance including cardiac 31P-spectroscopy. RESULTS: Participants were predominantly middle-age (64±11 years) women (97%). Although takotsubo cardiomyopathy occurred 20 (range 13-39) months before the study, the majority (88%) of patients had persisting symptoms compatible with heart failure (median of 13 [range 0-76] in the Minnesota Living with Heart Failure Questionnaire) and cardiac limitation on exercise testing (reduced peak oxygen consumption, 24±1.3 versus 31±1.3 mL/kg/min, P<0.001; increased VE/VCO2 slope, 31±1 versus 26±1, P=0.002). Despite normal left ventricular ejection fraction and serum biomarkers, patients with prior takotsubo cardiomyopathy had impaired cardiac deformation indices (reduced apical circumferential strain, ‒16±1.0 versus ‒23±1.5%, P<0.001; global longitudinal strain, ‒17±1 versus ‒20±1%, P=0.006), increased native T1 mapping values (1264±10 versus 1184±10 ms, P<0.001), and impaired cardiac energetic status (phosphocreatine/γ-adenosine triphosphate ratio, 1.3±0.1 versus 1.9±0.1, P<0.001). CONCLUSIONS: In contrast to previous perceptions, takotsubo cardiomyopathy has long-lasting clinical consequences, including demonstrable symptomatic and functional impairment associated with persistent subclinical cardiac dysfunction. Taken together our findings demonstrate that after takotsubo cardiomyopathy, patients develop a persistent, long-term heart failure phenotype. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov. Unique identifier: NCT02989454.