Severe Left Heart Research Articles

Disturbed myocardial connexin 43 and N-cadherin expressions in hypoplastic left heart syndrome and borderline left ventricle

Borderline left ventricle is the left ventricular morphology at the favorable end of the hypoplastic left heart syndrome. In contrast to the severe end, it is suitable for biventricular repair. Wondering whether it is possible to identify cases suitable for biventricular repair from a developmental viewpoint, we investigated the myocardial histology of borderline and severely hypoplastic left ventricles. Postmortem specimens of neonatal, unoperated human hearts with severe hypoplastic left heart syndrome and borderline left ventricle were compared with normal specimens and hearts from patients with transposition of the great arteries. After tissue sampling of the lateral walls of both ventricles, immunohistochemical and immunofluorescence stainings against cardiac troponin I, N-cadherin, and connexin 43, important for proper cardiac differentiation, were done. All severely hypoplastic left hearts (7/7) and most borderline left ventricle hearts (4/6) showed reduced sarcomeric expressions of troponin I in left and right ventricles. N-cadherin and connexin 43 expressions were reduced in intercalated disks. The remaining borderline left ventricle hearts (2/6) were histologically closer to control hearts. Four of 6 borderline left ventricle hearts showed myocardial histopathology similar to the severely hypoplastic left hearts. The remainder were similar to normal hearts. Our results and knowledge regarding the role of epicardial-derived cells in myocardial differentiation lead us to postulate that an abnormal epicardial-myocardial interaction could explain the observed histopathology. Defining the histopathologic severity with preoperative myocardial biopsy samples of hearts with borderline left ventricle might provide a diagnostic tool for preoperative decision making.

Role of FPR1 Formyl Peptide Receptors in the Cardioprotective Actions of Annexin-A1 Against Ischaemia–Reperfusion (I–R) Injury

M. Imran ∗, A. Keogh, E. Kotylar, C. Hayward, P. Macdonald, R. Prichard Heart Transplant Unit, St. Vincent’s Hospital, NSW, Australia Introduction: A high transpulmonary gradient (i.e. >10mmHg) secondary to severe left heart failure is associatedwith increasedmortality after heart transplantation and left ventricular assist device implantation. Endothelin receptor antagonists are useful in certain forms of pulmonary hypertension (PAH), but avoided in PAH due to LHF. In this small studywe assessed the effect of bosentan on right heart haemodynamics in LHF with high TPG. Methods: Four patients with advanced LHF and high TPG-unresponsive to vasodilator challenge with nitroglycerine infusion or inhaled nitric oxide (precluding transplant or LVAD) received bosentan (62.5mg or 125mg BD) supplied on compassionate usage by Actelion Pharmaceuticals Australia. Serial right heart catheterisations were performed. Results: One of four patients had no fall in TPG after six weeks therapy and bosentan was discontinued. Three of four patients showed a good response to bosentan. Patient #1: was on LVAD support, developed a TPG of 16mmHg, falling to <10 on bosentan allowing successful heart transplant at 2 months. Patient #2: three months bosentan therapy resulted in improvement inTPG from20 to 12mmHg, PVR from 421 to 218 dyne s cm−5 and cardiac 2 of the actions of full-length ANX-A1 and activates both formyl peptide receptor (FPR)1 and FPR2. Although their anti-inflammatory effects are largely mediated by FPR2, receptors responsible for ANX-A1-based cardioprotection have not been resolved. In this study, rat isolated hearts were Langendorff-perfused with physiological buffer at constant flow (10mL/min), subjected to global, no-flow 30-min ischaemia followed by 30-min reperfusion. Hearts (n= 6–8 per group) were randomly allocated to treatment during reperfusion with Ac-ANX-A12–26 (0.3 M) in absence or presence of either non-selective FPR1/FPR2 antagonist Boc-2 (10 M), FPR2-selective antagonist Quinc-7 (10 M) or FPR1-selective antagonist Cyclosporin-H (1 M). Upon reperfusion, LV developed pressure (LVDP) was significantly reduced compared to pre-ischaemic baseline, and remained depressed during reperfusion. Lactate dehydrogenase (LDH) release was significantly elevated during reperfusion compared to sham (p= 0.001). In comparison, Ac-ANX-A12–26 treated hearts elicited complete recovery of LVDP by 10min reperfusion (p< 0.01), and LDH release was significantly attenuated (p= 0.005). Interestingly, preservation of LV function and cell viability mediated by Ac-ANXA12–26 were prevented by Boc-2, partially attenuated by Cyclosporin-H, but were unaffected by Quinc-7. Our findings suggest administration of Ac-ANX-A12–26 on reperfusion rescues LV function likely via activation of index from 1.7 to 2.0 l/min/m . He remains under consideration for heart transplant. Patient #3: bosentan for six months resulted inTPGfall from27 to18mmHg,PVRfrom 424 to 300 dyne s cm−5 with improvement in symptoms. Conclusion: Bosentan therapy can diminish disproportionately elevated TPG, secondary to left heart failure, facilitating definitive therapy (LVAD implant or transplant). http://dx.doi.org/10.1016/j.hlc.2012.05.232

Mitral valve dysplasia syndrome: A unique form of left-sided heart disease

Mitral valve dysplasia syndrome is a unique form of left-sided heart disease characterized by aortic outflow hypoplasia, dilated left ventricle, dysplastic/incompetent mitral valve, and a restrictive/intact atrial septum. Patients with this constellation of abnormalities have been managed in a variety of ways with overall poor outcomes. We performed a retrospective review of all patients with mitral valve dysplasia syndrome to identify fetal echocardiographic markers predictive of outcomes. Mitral valve dysplasia syndrome was identified in 10 fetuses. Fetal left heart dilation and abnormal pulmonary venous flow were associated with increased mortality. Seven fetuses had abnormal pulmonary venous Doppler patterns; 3 had a unique "double-reversal" flow pattern. Severe fetal left heart dilation (left heart/right heart area ratio > 1.5) was present in 5. Prenatal intervention was performed on 3 fetuses: balloon aortic valvuloplasty (n=2) and balloon atrial septostomy (n=1). Of the 3, one died in utero and neither survivor underwent a 2-ventricle repair. Five patients required an immediate postnatal intervention to open the atrial septum. The overall mortality was 50%. Mitral valve dysplasia syndrome is a unique form of congenital heart disease with severe aortic stenosis but normal or enlarged left ventricle secondary to primary mitral valve disease. Increased left heart size and pulmonary vein Doppler patterns are predictive of postnatal outcome. Despite the presence of a dilated left ventricle, postnatal management with staged single ventricle palliation may be the most effective strategy.

A case of mitochondrial disease with severe left ventricular hypertrophy.

A 35-year-old woman was admitted for progressive dyspnea with lower limb edema. Transthoracic echocardiography showed severe left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction (HFPEF). Electron microscopy of an endomyocardial biopsy sample revealed a high density of mitochondria of abnormal size and shape. We report a case of mitochondrial disease with severe LVH and HFPEF.

Nursing of patients with severe acute left heart failure during emergent treatment with traumatic mechanical ventilation

目的 探讨机械通气治疗重度急性左心衰竭的护理措施,以提高患者的生存率.方法 分析29例常规治疗无效而加用有创性通气治疗的重度急性左心衰竭患者的临床资料,比较机械通气前后血气分析结果和病情情况,有针对性地进行护理干预.结果 29例患者中25例患者在24～96 h内成功撤机,总有效率86.2%;4例患者因原发病严重而死亡,其中2例因多脏器功能衰竭而死亡,2例因心源性休克而死亡,病死率13.8%.结论 机械通气治疗急性左心衰竭不仅见效快,且抢救成功率高,但在治疗过程中需全面、针对性护理,使患者顺利度过危险期,提高治疗的有效性和患者的生活质量。

Reconstruction complexe de la région mammaire après traumatisme thoracique grave par arme à feu

This case report is of a 47-year-old woman who suffered a ballistic chest trauma with severe left hemothorax and heart wound. She was treated in emergency for the collapse by heart surgery. Then the coverage for her soft thorax tissue loss was done by an ipsilateral musculocutaneous latissimus dorsi pedicled flap. The patient was subsequently addressed to our team for a repair, especially for reconstruction of the left breast. Initially, rehabilitation of aesthetics units breast was achieved through the realization of an abdominal advancement flap, and breast volume was restored by several sessions of lipomodeling. The surgical alternatives were very limited for this post-traumatic complex breast reconstruction. Due to ballistic trauma, no reliable recipient vessels allowed a microsurgical solution, and the ipsilateral latissimus dorsi was used for the coverage. In conclusion, the restoration of the aesthetics units with lipomodeling has achieved a very good result in this extreme thoracomammary region repair.

Clinical observation on treatment of 45 Cases of severe acute left heart failures with non-invasive mask ventilator

Objective To observe the clinical treatment of severe acute left heart failures with non-invasive mask ventilator. Methods All patients were conducted on common treatment of heart failure, including high concentration oxygen,tranquillizer,cardiac stimulant,diuretic,vasodilators and antispasmodic and asthma,etc. ,and mechanical ventilation with non-invasive mask ventilator is emergently applied to the patients whose state of illness could not be controlled. Results 35 cases were mitigated and the success rate up to 77.8% ;there were remarkable differences in pH values of arterial blood, PaO2, PaCO2, SaO2 and vital signs before and after ventilators were applied (P ＜ 0. 05). Conclusion The non-invasive mask ventilator was an effective measure for treatment of severe acute left heart failure. Key words: Ventilators, mechanical; Heart failure, congestive

Reversible congestive heart failure in severe hypocalcemia

We present a case of severe congestive left heart failure due to profound and long-term hypocalcemia caused by surgically induced hypoparathyroidism. Hypocalcemia as a potential contributor to heart failure should be included in the differential diagnosis of all patients with congestive heart failure who do not respond adequately to the usual treatment. By rapid correction of the serum calcium level unnecessary diagnostic and therapeutic measures might be avoided. In addition, being aware of and treating hypocalcemia is crucial since this kind of heart failure is completely reversible with calcium and vitamin D treatment.The pivotal role of calcium in molecular and cellular biology is well known, but its clinical importance in day-to-day practice is often underestimated. Although some cases of heart failure resulting from hypocalcemia secondary to hypoparathyroidism have been published in the last 20 years, this subject is still poorly documented in almost all current textbooks.

Near-infrared spectroscopy during stagnant ischemia estimates central venous oxygen saturation and mixed venous oxygen saturation discrepancy in patients with severe left heart failure and additional sepsis/septic shock

IntroductionDiscrepancies of 5-24% between superior vena cava oxygen saturation (ScvO2) and mixed venous oxygen saturation (SvO2) have been reported in patients with severe heart failure. Thenar muscle tissue oxygenation (StO2) measured with near-infrared spectroscopy (NIRS) during arterial occlusion testing decreases slower in sepsis/septic shock patients (lower StO2 deoxygenation rate). The StO2 deoxygenation rate is influenced by dobutamine. The aim of this study was to determine the relationship between the StO2 deoxygenation rate and the ScvO2-SvO2 discrepancy in patients with severe left heart failure and additional sepsis/septic shock treated with or without dobutamine.MethodsFifty-two patients with severe left heart failure due to primary heart disease with additional severe sepsis/septic shock were included. SvO2 and ScvO2 were compared to the thenar muscle StO2 before and during arterial occlusion.ResultsSvO2 correlated significantly with ScvO2 (Pearson correlation 0.659, P = 0.001), however, Bland Altman analysis showed a clinically important difference between both variables (ScvO2-SvO2 mean 72 ± 8%, ScvO2-SvO2 difference 9.4 ± 7.5%). The ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.400, P = 0.003) and the StO2 deoxygenation rate (Pearson correlation 0.651, P = 0.001). In the group of patients treated with dobutamine, the ScvO2-SvO2 difference correlated with plasma lactate (Pearson correlation 0.389, P = 0.011) and the StO2 deoxygenation rate (Pearson correlation 0.777, P = 0.0001).ConclusionsIn patients with severe heart failure with additional severe sepsis/septic shock the ScvO2-SvO2 discrepancy presents a clinical problem. In these patients the skeletal muscle StO2 deoxygenation rate is inversely proportional to the difference between ScvO2 and SvO2; dobutamine does not influence this relationship. When using ScvO2 as a treatment goal, the NIRS measurement may prove to be a useful non-invasive diagnostic test to uncover patients with a normal ScvO2 but potentially an abnormally low SvO2.Trial RegistrationNCT00384644 ClinicalTrials.Gov.

An Unusual Recovery following Aortic Valve Surgery

This case report describes the extraordinary recovery of Father Ronald Pytel from valvular cardiac disease. Father Pytel had developed severe left ventricular dysfunction and congestive heart failure from aortic valvular disease. Following aortic valve replacement surgery, his condition did not improve. Following a healing Mass on the Feast Day of Blessed Faustina Kowalska and through her intercession, he demonstrated a complete recovery. The doctors of the Sacred Congregation for the Cause of Saints voted that the sudden change from a severely damaged left ventricle of the heart to a normal functioning left ventricle cannot be explained by natural medical science. This case was used in the process of Saint Faustina's canonization.

Effects of noninvasive ventilation for treating postoperation acute left heart failure on arterial blood gas and pulmonary function

Objective To study the influence of noninvasive ventilation on pH, PaO2, PaCO2 in arterial blood gas and PEF, FEV1/FVC in pulmonary function of post-operation patients with moderate to severe acute left heart failure. Methods Forty cases of post-operation patients with acute left heart failure were randomly divided into two groups. One group was treated only by drugs (control group), the other group were treated by noninvasive ventilation and drugs (ventilation group). The changes of pH, PaO2, PaCO2 in the arterial blood gas before and after the treatment between the two groups were compared, and also the changes of PEF, FEV1/FVC in pulmonary function before and after treatment between the two groups were compared. Results Compared to control group, PaO2, PaO2/FiO2 were increased and PaCO2 decreased in the ventilation group, and also the PEF, FEV1/FVC were increased significantly in the ventilation group (P<0.05～0.01). Conclusion The use. of noninvasive ventilation in treating post-operation patients with acute left heart failure can decrease airway resistance and improve the oxygenation in lung. Key words: Noninvasive ventilation; Acute left heart failure; Pulmonary function

Reduced EGFR causes abnormal valvular differentiation leading to calcific aortic stenosis and left ventricular hypertrophy in C57BL/6J but not 129S1/SvImJ mice

Epidermal growth factor receptor (EGFR) signaling contributes to aortic valve development in mice. Because developmental phenotypes in Egfr-null mice are dependent on genetic background, the hypomorphic Egfr(wa2) allele was made congenic on C57BL/6J (B6) and 129S1/SvImJ (129) backgrounds and used to identify the underlying cellular cause of EGFR-related aortic valve abnormalities. Egfr(wa2/wa2) mice on both genetic backgrounds develop aortic valve hyperplasia. Many B6-Egfr(wa2/wa2) mice die before weaning, and those surviving to 3 mo of age or older develop severe left ventricular hypertrophy and heart failure. The cardiac phenotype was accompanied by significantly thicker aortic cusps and larger transvalvular gradients in B6-Egfr(wa2/wa2) mice compared with heterozygous controls and age-matched Egfr(wa2) homozygous mice on either 129 or B6129F1 backgrounds. Histological analysis revealed cellular changes in B6-Egfr(wa2/wa2) aortic valves underlying elevated pressure gradients and progression to heart failure, including increased cellular proliferation, ectopic cartilage formation, extensive calcification, and inflammatory infiltrate, mimicking changes seen in human calcific aortic stenosis. Despite having congenitally enlarged valves, 129 and B6129F1-Egfr(wa2/wa2) mice have normal lifespans, absence of left ventricular hypertrophy, and normal systolic function. These results show the requirement of EGFR activity for normal valvulogenesis and demonstrate that dominantly acting genetic modifiers curtail pathological changes in congenitally deformed valves. These studies provide a novel model of aortic sclerosis and stenosis and suggest that long-term inhibition of EGFR signaling for cancer therapy may have unexpected consequences on aortic valves in susceptible individuals.

Clinical observation of mechanical ventilation in treatment of acute severe left heart failure

Objective To explore the effects of mechanical ventilation on the treatment of acute severe left heart failure.Methods While the routine drug therapy was used,25 patients with severe acute left heart failure received mechanical ventilation treatment.The changes of their artery blood gas,vital signs and clinical symptom were observed before and after mechanical ventilation.Results The parameters of their blood gas and clinical symptom were dramatically improved after the mechanical ventilation therapy in 21 patients(P＜0.01).19 patients were saved successfully and 6 patients died.Conclusion The mechanical ventilation could effectively improve the clinical symptoms and respiratory function of patients with acute severe left heart failure,which is an effective method in the adjuvant treatment of patients with acute severe left heart failure. Key words: Venficular dysfunction,left; Respiration,artificial

Akute Herzinsuffizienz mit Lungenödem nach Sectio caesarea

Severe left heart failure shortly after delivery in a previously asymptomatic young woman can be caused by a peripartum cardiomyopathy, an exacerbation of valvular heart disease due to both congenital or acquired etiologies, a sustained chronic tachyarrhythmia (tachycardiomyopathy), a fulminant pulmonary embolism, or an infective endocarditis. 2 days following cesarean section, a 36-year-old primipara without known previous heart disease suffered from severe left heart failure with pulmonary edema (Figure 1) due to an acute bacterial aortic valve endocarditis. The infecting organisms were beta-hemolytic group A streptococci. After diagnosis could be confirmed by conventional Doppler echocardiography and by transesophageal echocardiography (Figures 2 and 3), the clinical situation of the patient stabilized in a few days under an initial antibiotic regimen with vancomycin and gentamicin, diuretics and catecholamines, followed by diuretics and ACE inhibitor. 14 days after cesarean delivery, aortic valve replacement could be performed under hemodynamically stable conditions. Although postpartal endocarditis is rarely described in the era of peripartum antibiotic prophylaxis, it should be considered in the differential diagnosis of patients with heart failure or fever in pregnancy, following delivery or cesarean section. The prognosis of peripartal endocarditis as a life-threatening disease is determined by an accurate and immediate diagnosis.

Risk factors for death and the 3-year survival of patients with systemic sclerosis: the French ItinerAIR-Sclerodermie study

Objectives. This longitudinal study investigated survival, risk factors and causes of death in the multicentre ItinérAIR-Sclérodermie cohort of patients with SSc without severe pulmonary fibrosis or severe left heart disease at baseline.Methods. At 3-year follow-up, vital status was obtained from investigators or French national death records. Causes of death were classified as SSc-related or otherwise. Data were censored at 37 months, time of death or loss to follow-up, whichever was earlier. Survival was estimated using the Kaplan–Meier method. Multivariate survival analyses were conducted using the Cox model.Results. In total, 546 patients were followed for a median duration of 37 months, representing 1547 patient-years. At baseline, the majority of patients were female, with lcSSc, mean age 54.9 ± 13.0 years and mean duration of SSc of 8.8 ± 8.1 years. In total, 47 patients died, giving a 3-year survival of 91.1% and cumulative mortality of 3.04 deaths per 100 patient-years; 17 deaths (32.2%) resulted from pulmonary arterial hypertension (PAH) and eight (17.1%) from cancer. Of the 47 patients with PAH at baseline, 20 died during follow-up, giving a 3-year survival of 56.3%. In a multivariate analysis, PAH [hazard ratio (HR) 7.246], age at first symptom (HR 1.052), duration of SSc (HR 1.047 per year) and Rodnan skin score (per one point) (HR 1.045) were associated with increased mortality.Conclusion. This 3-year study observed survival and mortality estimates that were comparable with previous reports. PAH increased the HR for mortality in patients with SSc, justifying yearly echocardiographic screening.

Levoatrial cardinal vein in mitral atresia and closed foramen ovale: prenatal diagnosis and perinatal management

A levoatrial cardinal vein is a rare cardiovascular anomaly that may be present in malformed hearts with severe left heart obstruction and restrictive interatrial communication. We report the prenatal diagnosis at 23 weeks of a fetus with mitral atresia, double-outlet right ventricle, premature closure of the foramen ovale and a levoatrial cardinal vein draining into the innominate vein. In a prior examination performed elsewhere the levoatrial cardinal vein had been interpreted as an aortic arch perfused retrogradely, and hypoplastic left heart syndrome with aortic atresia had been diagnosed. Prenatal management, induction at 38 weeks and postnatal examinations and treatment are reported. To the best of our knowledge, this is the first reported prenatal diagnosis of this embryological vessel, presenting a potential pitfall for prenatal echocardiography.

Pulmonary hypertension and left heart disease: emerging concepts and treatment strategies

At least two thirds of patients with chronic severe left heart disease have associated pulmonary hypertension, and mortality associated with biventricular failure is >two-fold higher compared with isolated left ventricular failure. This review considers and discusses emerging concepts and strategies from recent studies of specific treatments in populations with pulmonary hypertension complicating overt left ventricular dysfunction. While the results reported in the studies considered are encouraging, to date there are no large randomised studies of specific treatments in populations with pulmonary hypertension complicating overt left ventricular dysfunction.

Nitro plaster in coronary heart disease and severe left heart insufficiency

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

What's the Connection?

A 26-year-old white man presented to our referral hospital with a 1-month history of persistent cough productive of white sputum, which was occasionally tinged with blood. He reported mild pleuritic chest pain but no dyspnea, fever, chills, night sweats, or weight loss. The patient had had no epistaxis or episodes of sinusitis. One week before presentation, his cough had been treated with an empirical course of azithromycin with no resolution of his symptoms. A key feature when evaluating a patient with cough is symptom duration. Acute cough lasts less than 3 weeks and is usually caused by a respiratory tract infection. Cough lasting longer than 8 weeks is considered chronic and is most often due to postnasal drip, asthma, or gastroesophageal reflux disease. Hemoptysis, however, suggests diseases of the airways — particularly bronchitis and bronchiectasis, although other causes must also be considered. A young man is unlikely to have bronchogenic carcinoma, although he could have metastatic testicular cancer or bronchial carcinoid. Kaposi’s sarcoma involving the airways may cause hemoptysis in patients infected with the human immunodeficiency virus (HIV). Hemoptysis can also arise from the lung parenchyma. Autoimmune disease, cocaine inhalation, and infections (including tuberculosis, bacterial pneumonia, and lung abscess) are potential culprits. A last consideration is that hemoptysis can arise from the pulmonary vasculature as a result of pulmonary embolism, pulmonary arteriovenous malformation, mitral stenosis, and severe left heart failure. Five years before this presentation, the patient had been treated for a right-sided spontaneous pneumothorax. At that time, his hospital course was complicated by multiple chest-tube insertions on the right side, thoracotomy, and pleurodesis. Three years before presentation, he had had left-sided flank pain and was found to have a spontaneous left renal-artery dissection with renal infarction. He had received care elsewhere, and medical records were not available. The patient worked as a graphic designer. He was monogamous and had no risk factors for infection with HIV. He neither smoked nor used illicit drugs. His outpatient medications consisted only of a multivitamin. His mother died at 52 years of age from a presumed pulmonary embolus; the family history was otherwise unremarkable.

Metabolic effects of phosphodiesterase III inhibitors: another reason to promote their use?

Phosphodiesterase III inhibitors combine positive inotropic and vasodilator properties. These inhibitors are therefore frequently used to treat low cardiac output and/or severe left heart failure associated with cardiac surgery. Their effects on energy metabolism and visceral organ function are not well studied, however, particularly in comparison with their 'competitors' in daily practice (that is, catecholamines).