Signs Of Volume Overload Research Articles

Assessment of experimental circulating biomarkers in volume and pressure overload: insights from a cohort study

Abstract Introduction Experimental biomarkers including Angiopoietin-2 (ANG2), bone morphogenetic protein 10 (BMP10), fibroblast growth factor 23 (FGF23), and insulin-like growth factor-binding protein 7 (IGFBP7) are hypothesized to reflect cardiac pathophysiological processes that are potentially present in adverse cardiac remodeling in volume or pressure overload. This study aims to elucidate the relationship between these circulating biomarkers and the presence of hemodynamically significant pressure or volume overload and adverse outcomes and compare it to N-terminal pro B-type natriuretic peptide (NT-proBNP). Methods We studied the association between the four experimental circulating biomarkers in patients with pressure or volume overload with reference to none/mild valvular disease in N=1302 of an observational outpatient cardiology cohort. The median age was 63.0 (25th/75th quartile 51.5, 71.4) years, 445 (34.2%) were women. Circulating biomarkers were quantified using a novel antibody-based method. Logistic regression models with cox regression plots were employed to assess the association of each biomarker with the severity of valve disease concerning volume or pressure overload, adjusted for age and sex. Results In the overall population, elevated levels of ANG2, BMP10, FGF23 and IGFB7 were positively associated with the presence of significant volume overload (ANG2: Odds ratio (OR) 1.26 (95% confidence interval (CI) 1.17-1.35), p<0.001; BMP10: OR 2.57 (CI 1.89-3.48), p<0.001; FGF23: OR 1.51 (CI 1.14-1.20), p=0.004; IGFBP7: OR 1.39 (CI 1.14-1.69), p=0.001, NT-proBNP: OR 1.69 (CI 1.47-1.95), p<0.001). No statistically significant association between circulating biomarkers and pressure overload was observed. Over a median follow-up of 4 years, 31 (20.1%) participants died in the group of volume overload and 9 (40.9%) individuals in the group of pressure overload. After multivariable-adjustment, elevated levels of BMP 10 showed a borderline association with an increased risk of all-cause mortality in individuals with volume overload compared to none/mild valvular disease: hazard ratio (HR) 1.51 (CI 0.96- 2.38), p=0.075. Higher concentrations of all biomarkers were predictive of all-cause mortality for both individuals with volume overload and those with none/mild valvular disease (ANG2: HR 3.72 (CI 1.67-8.33), p=0.001; BMP10: HR 1.65 (CI 1.20-2.26), p=0.002; FGF23: HR 2.08 (CI 1.65-2.62), p<0.001; IGFBP7: HR 1.55 (CI 1.25-1.91), p<0.001; NT-proBNP: HR 1.72 (CI 1.47-2.00), p<0.001). Conclusions This study demonstrates that circulating biomarkers involved in distinct pathophysiological pathways of inflammation, fibrosis and calcification are elevated in patients with hemodynamically significant volume overload. Since they are also related to mortality, their clinical role needs to be explored further, also in context with the routine biomarker NT-proBNP.

Investigation of serum copeptin levels in patients with congestive heart failure

Aims: Congestive heart failure (CHF) is characterized by symptoms and signs of volume overload and tissue perfusion insufficiency and accompanied by neurohormonal activation. Copeptin is a part of pre-pro-vasopressin and synthesized in equal molar amounts with vasopressin. We aimed to evaluate the sensitivity and specificity of copeptin in indicating the diagnostic value of CHF Methods: This retrospective study included a total of 80 patients including 40 with heart failure and 40 healthy individuals. The groups were compared in terms of demographic features, laboratory findings including copeptin levels. Results: There was no statistically significant difference between the groups in terms of gender (p>0.05). Age, hypertension, diabetes mellitus, smoking were statistically significantly higher in the heart failure group compared to the control group (p<0.05). In both groups, serum copeptin levels were higher in men than in women. Copeptin levels in the heart failure group were statistically significantly higher than in the control group (p<0.05). In the heart failure group, there was a negative correlation between serum copeptin levels and age, gender, hypertension, smoking, HDL cholesterol, hematocrit, creatinine levels. Conclusion: Copeptin is a good indicator of the course of the disease in patients with heart failure.

Cardiac manifestations of Fabry disease in G3Stg/GlaKO and GlaKO mouse models-Translation to Fabry disease patients.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by mutations in the GLA gene encoding alpha-galactosidase A (α-Gal). Loss of α-Gal activity leads to progressive lysosomal accumulation of α-Gal substrate, predominately globotriaosylceramide (Gb3) and its deacylated derivative globotriaosylsphingosine (lyso-Gb3). FD manifestations include early onset neuropathic pain, gastrointestinal symptoms, and later onset life-threatening renal, cardiovascular and cerebrovascular disorders. Current treatments can preserve kidney function but are not very effective in preventing progression of cardiovascular pathology which remains the most common cause of premature death in FD patients. There is a significant need for a translational model that could be used for testing cardiac efficacy of new drugs. Two mouse models of FD have been developed. The α-Gal A-knockout (GlaKO) model is characterized by progressive tissue accumulation of Gb3 and lyso-Gb3 but does not develop any Fabry pathology besides mild peripheral neuropathy. Reports of minor cardiac function abnormalities in GlaKO model are inconsistent between different studies. Recently, G3Stg/GlaKO was generated by crossbreeding GlaKO with transgenic mice expressing human Gb3 synthase. G3Stg/GlaKO demonstrate higher tissue substrate accumulation and develop cellular and tissue pathologies. Functional renal pathology analogous to that found in early stages of FD has also been described in this model. The objective of this study is to characterize cardiac phenotype in GlaKO and G3Stg/GlaKO mice using echocardiography. Longitudinal assessments of cardiac wall thickness, mass and function were performed in GlaKO and wild-type (WT) littermate controls from 5-13 months of age. G3Stg/GlaKO and WT mice were assessed between 27-28 weeks of age due to their shortened lifespan. Several cardiomyopathy characteristics of early Fabry pathology were found in GlaKO mice, including mild cardiomegaly [up-to-25% increase in left ventricular (LV mass)] with no significant LV wall thickening. The LV internal diameter was significantly wider (up-to-24% increase at 9-months), when compared to the age-matched WT. In addition, there were significant increases in the end-systolic, end-diastolic volumes and stroke volume, suggesting volume overload. Significant reduction in Global longitudinal strain (GLS) measuring local myofiber contractility of the LV was also detected at 13-months. Similar GLS reduction was also reported in FD patients. Parameters such as ejection fraction, fractional shortening and cardiac output were either only slightly affected or were not different from controls. On the other hand, some of the cardiac findings in G3Stg/GlaKO mice were inconsistent with Fabry cardiomyopathy seen in FD patients. This could be potentially an artifact of the Gb3 synthase overexpression under a strong ubiquitous promoter. In conclusion, GlaKO mouse model presents mild cardiomegaly, mild cardiac dysfunction, but significant cardiac volume overload and functional changes in GLS that can be used as translational biomarkers to determine cardiac efficacy of novel treatment modalities. The level of tissue Gb3 accumulation in G3Stg/GlaKO mouse more closely recapitulates the level of substrate accumulation in FD patients and may provide better translatability of the efficacy of new therapeutics in clearing pathological substrates from cardiac tissues. But interpretation of the effect of treatment on cardiac structure and function in this model should be approached with caution.

Design and baseline characteristics of SALT-HF trial: hypertonic saline therapy in ambulatory heart failure.

Hypertonic saline solution (HSS) plus intravenous (IV) loop diuretic appears to enhance the diuretic response in patients hospitalized for heart failure (HF). The efficacy and safety of this therapy in the ambulatory setting have not been evaluated. We aimed to describe the design and baseline characteristics of the SALT-HF trial participants. 'Efficacy of Saline Hypertonic Therapy in Ambulatory Patients with HF' (SALT-HF) trial was a multicenter, double-blinded, and randomized study involving ambulatory patients who experienced worsening heart failure (WHF) without criteria for hospitalization. Enrolled patients had to present at least two signs of volume overload, use ≥ 80mg of oral furosemide daily, and have elevated natriuretic peptides. Patients were randomized 1:1 to treatment with a 1-h infusion of IV furosemide plus HSS (2.6-3.4% NaCl depending on plasmatic sodium levels) versus a 1-h infusion of IV furosemide at the same dose (125-250mg, depending on basal loop diuretic dose). Clinical, laboratory, and imaging parameters were collected at baseline and after 7days, and a telephone visit was planned after 30days. The primary endpoint was 3-h diuresis after treatment started. Secondary endpoints included (a) 7-day changes in congestion data, (b) 7-day changes in kidney function and electrolytes, (c) 30-day clinical events (need of IV diuretic, HF hospitalization, cardiovascular mortality, all-cause mortality or HF-hospitalization). A total of 167 participants [median age, 81years; interquartile range (IQR), 73-87, 30.5% females] were randomized across 13 sites between December 2020 and March 2023. Half of the participants (n=82) had an ejection fraction >50%. Most patients showed a high burden of comorbidities, with a median Charlson index of 3 (IQR: 2-4). Common co-morbidities included diabetes mellitus (41%, n=69), atrial fibrillation (80%, n=134), and chronic kidney disease (64%, n=107). Patients exhibited a poor functional NYHA class (69% presenting NYHA III) and several signs of congestion. The mean composite congestion score was 4.3 (standard deviation: 1.7). Ninety per cent of the patients (n=151) presented oedema and jugular engorgement, and 71% (n=118) showed lung B lines assessed by ultrasound. Median inferior vena cava diameter was 23mm, (IQR: 21-25), and plasmatic levels of N-terminal-pro-B-type natriuretic peptide (NTproBNP) and antigen carbohydrate 125 (CA125) were increased (median NT-proBNP 4969pg/mL, IQR: 2508-9328; median CA125 46U/L, IQR: 20-114). SALT-HF trial randomized 167 ambulatory patients with WHF and will determine whether an infusion of hypertonic saline therapy plus furosemide increases diuresis and improves decongestion compared to equivalent furosemide administration alone.

Not So Transient Effusive-Constrictive Pericarditis

A 63-year-old male patient presented with chest pain and signs of volume overload. His work-up revealed a diagnosis of transient effusive constrictive pericarditis of idiopathic etiology. Despite treatment with optimal medical therapy, he continued to experience persistent symptoms eventually requiring radical pericardiectomy.

Phenotyping congestion in acute heart failure by renal flow and right heart to pulmonary circulation coupling.

In acute heart failure (AHF), kidney congestion is basic to treatment and prognosis. Its aetiology is manifold and quite unexplored in details mainly regarding the right heart to pulmonary circulation (Pc) coupling. We investigated the right heart to kidney interrelationship by Doppler renal flow pattern, right atrial dynamics, and right ventricular (RV) function to Pc coupling in AHF. In 119 AHF patients, echocardiographic and renal Doppler data were analysed. Univariate and multivariate regression models were performed to define the determinants of a quantitative parameter of renal congestion, the renal venous stasis index (RVSI). When grouped according to different intra-renal venous flow patterns, no differences were observed in haemodynamics and baseline renal function. Nonetheless, patients with renal Doppler evidence of congestion showed a reduced RV function [tricuspid annular plane systolic excursion (TAPSE), S'-wave velocity, and fractional area change], impaired RV to Pc coupling [TAPSE/pulmonary artery systolic pressure (PASP) ratio], and right atrial peak longitudinal strain (RAPLS), along with signs of volume overload [increased inferior vena cava (IVC) diameters and estimated right atrial pressure]. Univariate and multivariate regression analyses confirmed TAPSE/PASP, RAPLS, and IVC diameter as independent determinants of the RVSI. RVSI was the only variable predicting the composite outcome (cardiac death, heart failure hospitalization, and haemodialysis). An easy-to-use echo-derived right heart score of four variables provided good accuracy in identifying kidney congestion. In AHF, the renal venous flow pattern combined with a right heart study phenotypes congestion and clinical evolution. Keys to renal flow disruption are an impaired right atrial dynamics and RV-Pc uncoupling. Integration of four right heart echocardiographic variables may be an effective tool for scoring the renal congestive phenotype in AHF.

Оценка технологии здравоохранения и значение дистанционного диэлектрического исследования в диагностикe и контроле лечения хронической сердечной недостаточности в Российской Федерации

As with any socially significant disease, in chronic heart failure (CHF), the control of diagnostic and treatment, including monitoring the condition of patients in order to maintain optimal therapy, is of decisive importance. The specificity of CHF is the high frequency of repeated hospitalizations for acute decompensation of heart failure (ADHF). One of the key aspects of monitoring the patient’s condition is the assessment of congestion - the identification and determination of the degree of it for the timely optimization of the treatment in order to prevent re-hospitalization. In this regard, of great interest is a new technology for non-invasive measurement of fluid in the lungs - Remote Dielectric Sensing (ReDS), implemented in a medical device under the ReDS Pro brand (manufacturer - Sensible Medical Innovations, Israel). ReDS technology is a quantitative non-invasive method for measuring the total volume of fluid in the lungs in patients with signs of volume overload, including those with CHF. The technology is based on the following principle: low-power electromagnetic radiation passes through the lung tissue from the emitter to the receiver, the assessment of changes in radio wave parameters provides an accurate measurement of the total volume of fluid in the tissue. The result of the examination is a quantitative indicator that reflects the percentage of total fluid in the total volume of the lung. The emergence of a new technology makes its assessment relevant for monitoring treatment and diagnostic measures for CHF in the Russian Federation at the inpatient and outpatient stages of medical care. The described study of health technology assessment was based on the developed model, which, taking into account the clinical advantages of ReDS technology, made it possible to analyze its “budget impact” both at the federal and regional levels from the standpoint of the inpatient or outpatient stages of medical care. The assessment of the economic and clinical feasibility of introducing ReDS tech- nology was carried out separately for the inpatient and outpatient stages (for the outpatient stage, the calculation was carried out both for a model that takes into account the costs of additional visits to patients for scheduled examinations, and without them) in conditions of achieving the technology availability indicator for at least 95% of the population. The results of the assessment showed that at a given level of implementation of ReDS technology at the inpatient level, the number of re-hospitalizations of patients with CHF in the Russian Federation will decrease from 375,703 to 252,208 per year (by 32.9%). The introduction of technologies at the outpatient level will reduce the number of readmissions from 375,703 to 82,782 per year (by 78.0%). This corresponds to a decrease in the annual cost of hospitalizations for CHF (both primary and recurrent) with the introduction of ReDS in hospitals from 24.93 billion rubles to 20.96 billion rubles (decrease by 15.9%); when implementing the method at the outpatient level from 24.93 billion rubles to 15.52 billion rubles (decrease by 37.8%), and taking into account the cost of additional visits to patients at the outpatient level from 24.93 billion rubles to 19.70 billion rubles (decrease by 21.0%). At the same time, one-time costs for the purchase of a ReDS medical device in outpatient and inpatient clinics amount to 12.06 billion rubles and 11.04 billion rubles respectively. The results of the “budget impact” analysis (taking into account the discount factor of 3.5%) of the introduction of ReDS technology at the outpatient level demonstrate that over 7 years it provides savings in the amount of 20,335,833,423 rubles (including costs for additional visits) up to 45,926,532,070 rubles (excluding the cost of additional visits), and at the inpatient level - 13,613,327,627 rubles. Evaluation of the introduction of ReDS technology into the Russian healthcare system at the federal level, both at the outpatient and inpatient stages of medical care, with a total need for a ReDS medical device in the range of 1129-1234 units, providing coverage of more than 95% of the population with this technology, showed its clinical and economic benefit, which is expressed in a decrease in the number of readmissions and net savings in the health care system already during the third year of using the ReDS technology.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

Introduction: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. Risk factors contributing to this condition are: advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, hypertension and In patients with gestational hypertension (GH) and other risk factors close monitoring is mandatory during pregnancy as well as in the postpartum period. Case report: A 38 year- old patient previously treated for endometriosis, infertility and GH was transferred from the Clinic of Gynecology due to diagnosed congestive heart failure. Five days prior admission she gave birth to her first child. Prior delivery she was treated with tocolytic therapy. She received methyldopa due to GH, that was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension (PAH) secondary to left ventricular failure. During hospitalization the patient was with signs of volume overload, but with well response on parenteral diuretic therapy. She was additionally treated with guideline recommended heart failure therapy. The controlled echocardiography showed improvement of the left ventricular function with an EF of 42%. Conclusion: PPCM is a rare condition with high morbidity and mortality. An LVEF <30%, marked LV dilatation, LV end-diastolic diameter >6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta trigger resolution of symptoms and recovery to the nonpregnant state of various organism, the contrary happens with blood pressure. Its peaking time is three to six days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy are a risk factor for PPCM due to causing decreased baroreflex sensitivity Patients with risk factors should be closely monitored for eventual cardiac complications.

540 RAGHIB SYNDROME WITH VERY LATE CLINICAL PRESENTATION.

Abstract A 72-year-old woman who had been diagnosed with pulmonary emphysema and permanent atrial fibrillation was admitted to our emergency department with signs and symptoms of heart failure (NYHA class III). Transthoracic echocardiography (TTE) revealed dilatation of both right and left atria, dilatation and systolic dysfunction of the right ventricle (RV) and severe pulmonary hypertension. Combined severe mitral and tricuspid regurgitation was also noted and, after clinical stabilization, transesophageal echocardiography (TEE) was performed to better assess valvular anatomy and function. TEE revealed clear evidence of a pre-tricuspid left-to-right shunt with signs of significant RV volume overload, but with difficulties in defining the characteristics of a suspected atrial septal defect (ASD). CMR confirmed the presence of a large coronary sinus ASD (Panel A) as responsible for a significant left-to-right shunt (Qp/Qs ∼ 3,5, measured by phase-contrast imaging after correcting for the combined mitral and tricuspid regurgitation; Panel B), as well as severe RV dilatation and dysfunction. Pulmonary venous drainage was normal. Persistent left superior vena cava (SVC; Panel C) draining directly into the left atrium (LA) and a completely unroofed coronary sinus were unveiled. The extremely rare combination of an unroofed coronary sinus with abnormal systemic venous drainage from double SVC circulation (usually as a persistent left SVC) is also known as Raghib syndrome (or Raghib complex). In the ASD with completely unroofed coronary sinus there is no common wall separating the coronary sinus from the LA, making the depiction of the shunt anatomy particularly difficult to assess with echocardiography. When unrecognized in the perinatal age, clinical natural course of Raghib syndrome can vary based on the severity of RV volume overload, and late (or very late) clinical presentations have been rarely reported. CMR, with its large field-of-view capability and multiparametric approach, provides accurate definition of cardiac and great vessels anatomy and function allowing the full non-invasive depiction of most congenital abnormalities. In many cases, multimodality imaging is the key to reach a full depiction of these complex conditions, particularly when adult patients with possible comorbidities need to be evaluated.

Early treatment with a sodium-glucose co-transporter 2 inhibitor in high-risk patients with acute heart failure: Rationale for and design of the EMPA-AHF trial

The aim of the EMPA-AHF trial is to clarify whether early initiation of a sodium-glucose co-transporter 2 inhibitor before clinical stabilization is safe and beneficial for patients with acute heart failure (AHF) who are at a high risk of adverse events. The EMPA-AHF trial is a randomized, double-blind, placebo-controlled, multicentre trial examining the efficacy and safety of early initiation of empagliflozin (10 mg once daily). In total, 500 patients admitted for AHF will be randomized 1:1 to either empagliflozin 10 mg daily or placebo at 47 sites in Japan. Study entry requires hospitalization for AHF with dyspnoea, signs of volume overload, elevated natriuretic peptide, and at least one of the following criteria: estimated glomerular filtration rate <60 mL/min/1.73 m2; already taking ≥40 mg of furosemide daily before hospitalization; and urine output of <300 mL within 2 hours after an adequate dose of intravenous furosemide. Patients will be randomized within 12 hours of hospital presentation, with treatment continued up to 90 days. The primary outcome is the clinical benefit of empagliflozin on the win ratio for a hierarchical composite endpoint consisting of death within 90 days, heart failure rehospitalization within 90 days, worsening heart failure during hospitalization, and urine output within 48 hours after treatment initiation. The EMPA-AHF trial is the first to evaluate the efficacy and safety of early initiation of empagliflozin in patients with AHF considered to be at high risk under conventional treatment.

Peripartum Cardiomyopathy Due to Gestational Hypertension and Tocolytic Therapy

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and sometimes fatal systolic heart failure that affects women during late pregnancy or the early postpartum period. The risk factors contributing to this condition are advanced maternal age, multiparity, administration of tocolytic agents, underlying cardiac disease, iatrogenic volume overload, preeclampsia, and hypertension. In patients with gestational hypertension (GH) and other risk factors, close monitoring is mandatory during pregnancy as well as in the postpartum period. CASE REPORT: A 38-year-old patient previously treated for endometriosis, infertility, and GH was transferred from the clinic of gynecology due to diagnosed congestive heart failure. 5 days before admission, she gave birth to her first child. Before delivery, she was treated with tocolytic therapy. She received methyldopa due to GH which was abruptly discontinued after her delivery. Echocardiography on admission revealed moderately reduced left ventricular (LV) systolic function with an ejection fraction (EF) of 37% with dilated left ventricle (LV) and pulmonary artery hypertension secondary to LV failure. During hospitalization, the patient was with signs of volume overload, but with a good response on parenteral diuretic therapy. She was additionally treated with guideline-recommended heart failure therapy. The controlled echocardiography showed improvement of LV function with an EF of 42%. CONCLUSION: PPCM is a rare condition with high morbidity and mortality. An LVEF &lt;30%, marked LV dilatation, LV end-diastolic diameter &gt;6.0 cm, and RV involvement are associated with adverse outcomes. Although delivery of the fetus and the placenta triggers the resolution of symptoms and recovery to the nonpregnant state of various organisms, the contrary happens with blood pressure. Its peak time is 3–6 days after delivery. Hypertension medication must not be immediately terminated. Prolonged tocolytic therapy is a risk factor for PPCM due to causing decreased baroreflex sensitivity. Patients with risk factors should be closely monitored for eventual cardiac complications.

Dealing With Failure.

Dealing With Failure.

Abstract 56: Differences Between Chronic Thromboembolic Disease And Chronic Thromboembolic Pulmonary Hypertension Patients At Time Of Presentation

Background: Approximately 1/3 of acute pulmonary embolism (PE) patients develop chronic thromboembolic disease (CTED), a condition in which a patient’s PE does not resolve after standard anticoagulation therapy. Chronic thromboembolic pulmonary hypertension (CTEPH) can occur in about 3-4% of acute PE patients. Though CTED and CTEPH share an underlying cause, few studies have compared symptom severity, patient history, and other clinical indicators for the two diseases. Moreover, CTED is sometimes considered to be an asymptomatic condition. The symptomatology in CTEPH is thought to be primarily determined by pulmonary hypertension, a characteristic that CTED patients do not share. Methods: Data were collected at baseline diagnosis from 24 CTED and 65 CTEPH patients in the University of Michigan Pulmonary Hypertension Registry between 2016-2020. Demographic, 6-minute walk (6MW), echocardiography, past medical history, and brain natriuretic peptide (BNP) data were compared between groups. Results: CTED patients were: 1) less symptomatic (better WHO functional class [FC], better predicted 6MW), 2) had more preserved oxygenation during 6MW, 3) had less RV dilation/dysfunction and RA dilation on echo, and 4) lower BNP, than CTEPH patients. Despite this, 54% of CTED patients demonstrated significantly impaired FC (III/IV) without evidence of significant RV dysfunction, exercise hypoxia or volume overload. Conclusion: More than half of CTED patients in our study had significantly impaired FC. Further investigation into CTED symptomatology is warranted. CTEPH patients are more symptomatic and present with worse clinical metrics than CTED patients, which may be attributed to more advanced RV dysfunction and higher BNP level. These results may help distinguish CTED v. CTEPH diagnoses earlier, leading to earlier targeted treatment and better outcomes.

Covid-19 Associated Lymphocytic Myocarditis With Genetic Predisposition

IntroductionThere is a possible association between lymphocytic myocarditis and COVID-19 in patients genetically susceptible to cardiomyopathy.CaseA 50-year-old female with history of hypertension and a family history of sudden cardiac death in two siblings and COVID-19 related myocarditis in a brother presented with persistent shortness of breath at rest, orthopnea, exertional stabbing-type chest pain, and fatigue two weeks after diagnosis of COVID-19. Physical exam was notable for tachycardia, with no fever or signs of volume overload. Patient was found to have elevated troponin and erythrocyte sedimentation rate, with normal brain natriuretic peptide and c-reactive protein. Electrocardiogram showed sinus tachycardia. Computer tomography angiography of the chest was negative for pulmonary embolism, pneumonia, or interstitial lung disease. Echocardiogram revealed lateral wall hypokinesis with ejection fraction 50% and normal ventricular cavity size. Coronary angiogram revealed normal coronaries. Cardiac magnetic resonance revealed anterolateral wall hypokinesis and left ventricular ejection fraction 45% with no scar or edema and no evidence of myocardial or pericardial disease.The patient received treatment with NSAIDs, furosemide, carvedilol, and colchicine. Symptoms persisted over the next several months. Magnetic resonance FDG-PET revealed increased uptake in the lateral wall of the left ventricle. Subsequent biopsy of this region revealed lymphocytic myocarditis. The patient was started on prednisone 60 mg, with partial improvement of symptoms. Symptomatic treatment also required acetaminophen and aspirin, with continued use of colchicine. Genetic studies revealed a likely pathogenic variant in the MYBPC3 gene involving an altered consensus splice site associated with autosomal dominant hypertrophic cardiomyopathy and dilated cardiomyopathy. Symptoms recurred upon tapering of prednisone, requiring a longer course of treatment. The patient also developed symptoms of postural orthostatic tachycardia syndrome. With continued treatment, symptoms significantly improved.ConclusionOur case suggests that lymphocytic myocarditis could be a rare manifestation of coronavirus disease whose risk factors may include hereditary cardiomyopathies. It has potential to become a chronic condition with a challenging symptomatic management.

Replacement myocardial fibrosis in patients with mitral valve prolapse. Relation to mitral regurgitation, ventricular remodeling and arrhythmia

Left ventricular (LV) replacement myocardial fibrosis has been described in MVP. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) in MVP Four hundred patients (53 ± 15 years, 55% male) with MVP underwent echocardiography and CMR. Correlates of replacement myocardial fibrosis (LGE + ), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events. LGE+ was observed in 110 patients (28%; 91 myocardial wall including 71 basal inferolateral wall, 29 papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45 vs. 26%, P < 0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass [OR 1.01, 95% CI (1.002–1.017), P = 0.009] and moderate-severe MR [OR: 2.28, 95% CI (1.21–4.31), P = 0.011]. LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6 ± 11.7 in LGE+ vs. 73.3 ± 6.5% in LGE-, P < 0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ [HR: 2.6 (1.4–4.9), P = 0.002] were associated with poor outcome ( Fig. 1 ). LV replacement myocardial fibrosis is frequent in patients with MVP, is associated with mitral valve apparatus alteration, more dilated LV, MR grade, ventricular arrhythmia, and is independently associated with cardiovascular events. These findings suggest a MVP-related myocardial disease. Finally, CMR provides additional information to echocardiography in MVP.

Replacement Myocardial Fibrosis in Patients With Mitral Valve Prolapse: Relation to Mitral Regurgitation, Ventricular Remodeling, and Arrhythmia.

Mitral valve prolapse (MVP) is a frequent disease that can be complicated by mitral regurgitation (MR), heart failure, arterial embolism, rhythm disorders, and death. Left ventricular (LV) replacement myocardial fibrosis, a marker of maladaptive remodeling, has been described in patients with MVP, but the implications of this finding remain scarcely explored. We aimed at assessing the prevalence, pathophysiological and prognostic significance of LV replacement myocardial fibrosis through late gadolinium enhancement (LGE) by cardiac magnetic resonance in patients with MVP. Four hundred patients (53±15 years of age, 55% male) with MVP (trace to severe MR by echocardiography) from 2 centers, who underwent a comprehensive echocardiography and LGE cardiac magnetic resonance, were included. Correlates of replacement myocardial fibrosis (LGE+), influence of MR degree, and ventricular arrhythmia were assessed. The primary outcome was a composite of cardiovascular events (cardiac death, heart failure, new-onset atrial fibrillation, arterial embolism, and life-threatening ventricular arrhythmia). Replacement myocardial fibrosis (LGE+) was observed in 110 patients (28%; 91 with myocardial wall including 71 with basal inferolateral wall, 29 with papillary muscle). LGE+ prevalence was 13% in trace-mild MR, 28% in moderate MR, and 37% in severe MR, and was associated with specific features of mitral valve apparatus, more dilated LV and more frequent ventricular arrhythmias (45% versus 26%, P<0.0001). In trace-mild MR, despite the absence of significant volume overload, abnormal LV dilatation was observed in 16% of patients and ventricular arrhythmia in 25%. Correlates of LGE+ in multivariable analysis were LV mass (odds ratio, 1.01 [95% CI, 1.002-1.017], P=0.009) and moderate-severe MR (odds ratio, 2.28 [95% CI, 1.21-4.31], P=0.011). LGE+ was associated with worse 4-year cardiovascular event-free survival (49.6±11.7 in LGE+ versus 73.3±6.5% in LGE-, P<0.0001). In a stepwise multivariable Cox model, MR volume and LGE+ (hazard ratio, 2.6 [1.4-4.9], P=0.002) were associated with poor outcome. LV replacement myocardial fibrosis is frequent in patients with MVP; is associated with mitral valve apparatus alteration, more dilated LV, MR grade, and ventricular arrhythmia; and is independently associated with cardiovascular events. These findings suggest an MVP-related myocardial disease. Last, cardiac magnetic resonance provides additional information to echocardiography in MVP.

Analysis of Noninvasive Ventilation in Subjects With Sepsis and Acute Respiratory Failure.

Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure (n = 70) and NIV success (n = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; P = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; P = .007), and initial NIV [Formula: see text] settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; P = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, P = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], P = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], P < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, P = .02) or had signs of volume overload (36% vs 64%, P < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], P = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], P = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], P = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], P = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], P < .001), and initial [Formula: see text] on NIV (odds ratio 1.04 [95% CI 1.01-1.08, P = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial [Formula: see text] settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.

Left heart dimensions in anemic cats and dogs before and after blood transfusion.

BackgroundWhether anemic cats and dogs with increased left heart dimensions are at higher risk of transfusion‐associated circulatory overload, and the effect of blood transfusion on left heart dimensions in naturally occurring anemia is unknown.Hypothesis/objectivesTo evaluate the effect of blood transfusion on left heart dimensions in clinically relevant anemia.AnimalsTwenty dogs and 20 cats presenting to a university veterinary teaching hospital.MethodsIn this prospective observational study, anemic dogs and cats requiring blood transfusion were included. Packed cell volume (PCV), total solids, and echocardiography were performed before and within 24 hours of blood transfusion. Signalment, bodyweight, disease process, transfusion duration and volume, and prior treatments were recorded. Nonparametric statistics were reported as median [range]. Post hoc Bonferroni correction set significance at P < .006.ResultsAfter transfusion, PCV increased in cats (12% [6–16] to 18% [10‐33], P = .001) and dogs (14% [7–24] to 25% [9‐37], P = .001), heart rate decreased in dogs (104 bpm [86‐166] to 87 bpm [56‐138], P < .001), and fractional shortening decreased in cats (57.1% [36.0‐84.7] to 41.0% [28.1‐69.6], P = .002) and dogs (33.79% [19.33‐62.79] to 31.89% [19.06‐51.47], P = .006). Left ventricular internal diameter in systole increased in cats (6.5 mm [2.7‐9.8] to 7.9 mm [5.3‐11.1], P = .001). Normalized left ventricular internal diameter in diastole (1.48 [1.25‐1.79] to 1.57 [1.33‐2.00], P = .001) and systole (0.87 [0.58‐1.19] to 1.00 [0.74‐1.36], P = .001) increased in dogs. Incidence of volume overload did not differ before (14/20 cats, 70%; 9/20 dogs, 45%) or after (12/20 cats, 60%; 11/20 dogs, 55%) transfusion (P = .64).Conclusions and clinical importanceBlood transfusion is well tolerated when signs of volume overload are present before transfusion.

Increased extracellular water measured by bioimpedance analysis and increased serum levels of atrial natriuretic peptide in polymyalgia rheumatica patients : Signs of volume overload.

Water retention is atypical feature of acute inflammatory episodes, chiefly implemented by the sympathetic nervous system (SNS) and the hypothalamic-pituitary-adrenal (HPA) axis. This is an important compensatory mechanism counteracting expected water loss, e.g., due to sweating. Both the SNS and HPA axis are activated in polymyalgia rheumatica (PMR). As retention mechanisms may similarly apply in this disease, we hypothesized increased water retention in PMR. Using bioimpedance analysis body composition was investigated in 64 healthy controls and 32 treatment-naive PMR patients. All PMR patients satisfied the 2012 EULAR/ACR classification criteria for PMR. 32 PMR patients were tested before and after 7 days of glucocorticoid-based therapy. Serum levels of pro-atrial natriuretic peptide (proANP) were investigated in all PMR patients and 15 healthy controls. Extracellular water (ECW) was markedly higher in PMR patients than in controls (mean ± SD: 49.1 ± 6.0% versus 36.3 ± 2.5% of total body water, p < 0.001). Patients with PMR demonstrated significantly higher serum levels of proANP compared to controls. Even before glucocorticoid treatment was initiated, systolic and diastolic blood pressure were higher in PMR patients compared to controls. Extracellular water levels did not change in PMR patients upon 7 days of intensified treatment. This study demonstrated increased extracellular water and elevated serum levels of proANP as signs of fluid overload in patients with PMR. Volume changes are imprinted as long-lasting mechanisms as water distribution is not affected by short-term anti-inflammatory therapy.

OptiVol for Volume Assessment in Patients With Continuous Flow Left Ventricular Assist Device.

OptiVol (Medtronic PLC, Minneapolis, MN) is a diagnostic feature of some cardiac implantable electronic devices (CIEDs) based on changes in thoracic impedance (TI) over time. Changes in TI can predict heart failure (HF) hospitalizations and mortality in HF populations. However, the utility of this feature is unknown in patients with a left ventricular assist device (LVAD). To determine if OptiVol and TI correlate with clinical HF events in a population of LVAD patients, hospitalization outcomes were collected retrospectively from the electronic health records at a single academic medical center in 80 LVAD patients with an OptiVol-capable CIED. Demographics, medical history, and available clinical data were reviewed and reported. The primary outcomes of interest were TI and OptiVol trends before and after hospitalization, and association of trends before and after these events was evaluated. Most patients had a HeartMate II LVAD and most CIEDs were defibrillators, and 23 (29%) had at least one HF hospitalization during the study period. HF hospitalizations were preceded by signs of volume overload in Optivol (60%) and TI (78%) with recovery of these measures post hospitalization in 33% and 25% of patients, respectively. Monitoring of TI and OptiVol may be one effective component of HF management in LVAD patients as part of a comprehensive program.