Cardiac Valvular Insufficiency Research Articles

Hemodynamic Effects of Sacubitril/Valsartan in Patients with Reduced Left Ventricular Ejection Fraction Over 24 Months: A Retrospective Study.

BackgroundThe effects of sacubitril/valsartan in patients with chronic heart failure with reduced ejection fraction (HFrEF) were recently reported. However, the hemodynamic impact of this well-established treatment in patients with HFrEF has been poorly systematically researched.AimWe aimed to investigate the hemodynamic effects of sacubitril/valsartan among patients with HFrEF.MethodsBetween 2016 and 2020, we retrospectively collected data for patients with HFrEF treated at the University Medical Center Mannheim, Germany. Data for 240 patients with HFrEF were available. We systematically analyzed echocardiographic parameters, all-cause hospitalization, and congestion rate.ResultsThe left ventricular ejection fraction (LVEF) improved from a median (minimum; maximum) of 28% (3; 65) before initiation of sacubitril/valsartan to a median of 34% (13; 64) at 24-month follow-up (p < 0.001). Systolic pulmonary atrial pressure (PAPsys) decreased from a median of 30 mmHg (13; 115) to 25 mmHg (20; 80) at 24-month follow-up (p = 0.005). The median (minimum; maximum) tricuspid annular plane systolic excursion improved from 17 mm (3; 31) at baseline to 20 mm (9; 30) at 12-month follow-up (p = 0.007). The incidence of severe and moderate mitral, tricuspid, and aortic valvular insufficiency improved after treatment. Hospitalization and congestion rates reduced at 24-month follow-up. The mortality rate in echocardiographic and functional nonresponders was higher than in responders (12.1 vs. 5.2%; p = 0.1 and 11.3 vs. 3.1%; p = 0.01, respectively).ConclusionFollow-up 24 months after starting treatment with sacubitril/valsartan revealed sustained improvements in echocardiographic parameters, including LVEF, PAPsys, and cardiac valvular insufficiency. Rates of all-cause hospitalization and congestion had decreased significantly at follow-up. The mortality rate was higher in echocardiographic and functional nonresponders.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40256-022-00525-w.

Functional Mitral Stenosis: A Result of Bacterial Endocarditis

A 72-year-old man presented with non-ST elevation myocardial infarction and received a drug eluting stent to mid RCA. Subsequent transthoracic echocardiogram demonstrated moderate mitral stenosis (MS) and a presumed rheumatic valve. He represented two weeks later with rigors and congestive cardiac failure. There was no peripheral stigmata of infective endocarditis (IE) but Streptococcus sanguinis (viridans) was grown in his blood cultures within 20 hours. Transoesophageal echocardiogram (TOE) revealed a large anterior mitral valve vegetation causing functional MS and he received a mechanical mitral valve replacement five days after diagnosis. IE classically results in cardiac valvular insufficiency. As it is rare for IE to cause functional or obstructive stenosis it is often not suspected clinically until later in its disease process and most of these cases occur in patients with pre-existing MS. This may occur if inflammation is confined to the surface of the valve causing endothelial damage whilst preserving tissue architecture. The resultant deposition of fibrin and platelets propagates further vegetation and aggregation. With bacterial growth the vegetations enlarge eventually becoming obstructive, leading to valvular stenosis. Valvular stenosis secondary to IE is challenging to treat medically and invariably leads to emergent surgery therefore early diagnosis and treatment are crucial. TOE is the current accepted diagnostic investigation. Heart failure secondary to valvular disease is the most common cause of death and therefore appreciation for early surgery is crucial for a good outcome.

Transudative Chylothorax in a Patient with Pulmonary Hypertension

Introduction: Chylothorax is defined by the presence of chyle in the pleural space. Transudative chylothorax has been reported between %15 - %32 of all chylothorax cases. In this report, we present a case of transudative chylothorax possibly developed from pulmonary hypertension due to cardiac valvular insufficiency and right heart failure. Case Presentation: A seventy years old, female patient admitted to our hospital with symptoms of dyspnea, right-sided chest pain for last 6 months. On chest radiography, pleural effusion covering nearly half of the right hemithorax was observed. Closed chest tube drainage was performed for relieving excessive pleural effusion. Since the color of pleural effusion appeared to be milky, pleural effusion was evaluated biochemically for chylothorax. Triglyceride level was found three fold higher than normal, but pleural effusion was transudative. Discussion: Chylothorax does not always meet the exudative criteria. Transudative form has been reported between %15-32 in several studies due to various pathologies. Since now, only two cases of transudative chylothorax due to pulmonary hypertension secondary to right heart failure have been reported. The possible mechanism for transudative chylothorax is poorly understood. Although very rare, evaluation of transudative pleural effusion for chylothorax should be considered in any patient with pulmonary hypertension with pleural effusion in clinical practice.

Adverse effects of benfluorex on heart valves and pulmonary circulation.

Benfluorex is responsible for the development of restrictive valvular regurgitation due to one of its metabolites, norfenfluramine. The 5-HT2B receptor, expressed on heart valves, acts as culprit receptor for drug-induced valvular heart disease (VHD). Stimulation of this receptor leads to the upregulation of target genes involved in the proliferation and stimulation of valvular interstitial cells through different intracellular pathways. Valve lesions essentially involve the mitral and/or aortic valves. The randomised prospective REGULATE trial shows a threefold increase in the incidence of valvular regurgitation in patients exposed to benfluorex. A cross-sectional trial shows that about 7% of patients without a history of VHD previously exposed to benfluorex present echocardiographic features of drug-induced VHD. The excess risks of hospitalisation for cardiac valvular insufficiency and of valvular replacement surgery were respectively estimated to 0.5 per 1000 and 0.2 per 1000 exposed patients per year. Recent data strongly suggest an aetiological link between benfluorex exposure and pulmonary arterial hypertension (PAH). The PAH development may be explained by serotonin, which creates a pulmonary vasoconstriction through potassium-channel blockade. Further studies should be conducted to determine the subsequent course of benfluorex-induced VHD and PAH, and to identify genetic, biological and clinical factors that determine individual susceptibility to developing such adverse effects.

Benfluorex and valvular heart disease: a cohort study of a million people with diabetes mellitus

To evaluate and quantify in diabetic patients treated with benfluorex in France, a fenfluramine-derivated product, a possible increase in risk of valvular heart disease, previously suggested by several published case reports. This was a French comparative cohort study using data from two large national linked databases, health insurance system (SNIIRAM) and hospitalization (PMSI). Patients aged 40-69 years with reimbursement for oral antidiabetic and/or insulin in 2006 were eligible. Exposed patients were defined as patients with at least one benfluorex reimbursement in 2006. Selected admission diagnoses of interest in 2007 and 2008 PMSI databases were valvular insufficiency for any cause, mitral insufficiency, aortic insufficiency, and valvular replacement surgery with cardiopulmonary bypass. Relative risks (RR) were adjusted on gender, age, and history of chronic cardiovascular disease. A total of 1,048173 diabetic patients were included, with 43,044 (4.1%) exposed to benfluorex. The risk of hospitalization in 2007 and 2008 for any cardiac valvular insufficiency was higher in the benfluorex group: crude RR=2.9 [95% confidence interval 2.2-3.7] and adjusted RR=3.1 [2.4-4.0], with a lower risk for patients with lower cumulative dose of benfluorex. Adjusted RR for mitral insufficiency and aortic insufficiency admissions were 2.5 [1.9-3.7] and 4.4 [3.0-6.6], respectively. Adjusted RR for valvular replacement surgery was 3.9 [2.6-6.1]. Benfluorex in diabetic patients was significantly associated with hospitalization for valvular heart disease in the 2 years following benfluorex exposure. Linkage between SNIIRAM and PMSI databases is in France a valuable tool to quantify the risk of serious adverse drug reactions.

Treatment of High Output Cardiac Failure by Flow-Adapted Hepatic Artery Banding (FHAB) in Patients with Hereditary Hemorrhagic Telangiectasia

Involvement of abdominal organs in Osler’s disease may lead to the development of hepatic arteriovenous shunts with a dilatation of the hepatic artery. Right and subsequent global heart failure due to cardiac valvular insufficiency, pulmonary artery hypertension, and hepatomegaly as well as increased cardiac output may result. This hyperdynamic hepatic blood flow can be reduced by ligature or banding of the hepatic artery or by orthotopic liver transplantation. We report on two female patients suffering from Osler’s disease (68 and 76 years old) with severe heart insufficiency (NYHA III-IV) caused by the high hepatic shunt volumes. A gradual banding of the hepatic artery directed by intraoperative flow measurement in the hepatic artery and control of the systemic hemodynamics by Swan–Ganz or COLD catheters was performed in these patients. The banding was achieved by encasing the hepatic artery in a PTFE cuff (length, 1.0 cm). The high cardiac output could be reduced from 11.2 to 7.0 l/min and from 10.7 to 6.0 l/min, respectively. The respective hepatic artery flow was reduced from 2.0 to 0.3 l/min and from 4.0 to 0.7 l/min. An improvement of heart insufficiency, a reduction in the severity of the cardiac valvular insufficiency, and a reduction of the pulmonary arterial hypertension could be already observed intraoperatively. One patient died of right cardiac failure after an orthotopic liver transplantation 7 months later. The other one died 3 years after the banding. The banding of the hepatic artery controlled by hepatic arterial flow measurement can be considered as an effective and safe palliative procedure in intrahepatic HHT compared to therapeutic alternatives such as hepatic artery ligation or embolization.

The potential use of selective 5-HT2C agonists in treating obesity

Activation of central 5-HT2C receptors as a strategy for appetite suppression and weight control is supported by animal pharmacology and human clinical studies. Considerable evidence comes from the weight-loss effects of fenfluramine, a non-selective 5-HT2C agonist. Advances in molecular pharmacology have led to an understanding of the effects of 5-HT2C receptor activation on food intake and satiety, in addition to providing insight into the causes of cardiac valvular insufficiency and pulmonary hypertension associated with the use of fenfluramine. However, clinically validated animal models of drug-induced disease and knowledge of the molecular mechanisms of these safety issues is lacking. For this reason, the development of selective 5-HT2C agonists for the treatment of obesity has remained a challenge.

The role of the polycystins in kidney development.

Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disease that affects both adults and children. Renal cysts are the cardinal sign of the disease that also causes cysts in liver, pancreas, testis, and ovary, as well as cardiac valvular insufficiency and arterial aneurysms. At least three genes cause ADPKD in humans. PKD1 and PKD2 have been cloned and sequenced, both code for novel proteins. Analyses of their primary structures suggest that polycystin-1, the PKD1 gene product, is a receptor, while similarities between the polycystins and calcium channel subunits suggest that these proteins are subunits of a novel channel. Individuals with mutations in PKD1 or PKD2 have identical phenotypes, which present at a later age in PKD2 patients. Recent evidence suggests that the two polycystins interact, providing a biochemical basis for the similarity of disease caused by mutations in PKD1 and PKD2. Consistent with its protean manifestations, polycystin-1 is widely expressed in both epithelial and nonepithelial tissues during embryological development. Mice with targeted mutations of either the PKD1 or the PKD2 genes die during embryogenesis. Thus, the PKD genes are required for normal fetal development. The observation that loss of polycystin-1 or -2 function causes death during embryogenesis suggests that PKD1 and PKD2 might be part of a morphoregulatory pathway.

The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetitie-Suppressant Drugs

The Prevalence of Cardiac Valvular Insufficiency Assessed by Transthoracic Echocardiography in Obese Patients Treated with Appetitie-Suppressant Drugs

The prevalence of cardiac valvular insufficiency assessed by transthoracic echocardiography in obese patients treated with appetite-suppressant drugs.

After case reports of cardiac-valve abnormalities related to the use of appetite suppressants were published, we undertook a study to determine the prevalence of the problem using transthoracic echocardiography. We examined patients who had taken dexfenfluramine alone, dexfenfluramine and phentermine, or fenfluramine and phentermine for various periods. We enrolled obese patients who had taken or were taking these agents during open-label trials from January 1994 through August 1997. We also recruited subjects who had not taken appetite suppressants and who were matched to the patients for sex, height, and pretreatment age and body-mass index. The presence of cardiac-valve abnormalities, defined by the Food and Drug Administration and Centers for Disease Control and Prevention as at least mild aortic-valve or moderate mitral-valve insufficiency, was determined independently by at least two cardiologists. Multivariate logistic-regression analysis was used to identify factors associated with cardiac-valve abnormalities. Echocardiograms were available for 257 patients and 239 control subjects. The association between the use of any appetite suppressant and cardiac-valve abnormalities was analyzed in a final matched group of 233 pairs of patients and controls. A total of 1.3 percent of the controls (3 of 233) and 22.7 percent of the patients (53 of 233) met the case definition for cardiac-valve abnormalities (odds ratio, 22.6; 95 percent confidence interval, 7.1 to 114.2; P<0.001). The odds ratio for such cardiac-valve abnormalities was 12.7 (95 percent confidence interval, 2.9 to 56.4) with the use of dexfenfluramine alone, 24.5 (5.9 to 102.2) with the use of dexfenfluramine and phentermine, and 26.3 (7.9 to 87.1) with the use of fenfluramine and phentermine. Obese patients who took fenfluramine and phentermine, dexfenfluramine alone, or dexfenfluramine and phentermine had a significantly higher prevalence of cardiac valvular insufficiency than a matched group of control subjects.

Infantile scoliosis in Marfan syndrome.

A retrospective review of clinical data was conducted. To determine the characteristics of infantile scoliosis in Marfan syndrome and the response to treatment of patients with this condition. No previous study has reported the features of this condition nor the effect of treatment on patients with this syndrome. The data on all patients seen at one institution who had Marfan syndrome and scoliosis by age three were reviewed. Fourteen of the 600 patients from the group examined who had Marfan syndrome fit the above criteria. Skeletal and general features were studied. Thirteen of the 14 patients had no family history of Marfan syndrome, a finding which does not fit the usual autosomal dominant inheritance pattern. All 14 patients had exaggeration of the Marfan. All but one patient had cardiac valvular insufficiency that required repair by age 11. Thirteen patients had thoracic aortic aneurysm, 10 had lens dislocation, and eight had sternal deformity. Three patients had hip dislocations, two had pyloric stenosis, and two had dural ectasia. Motor delay was evidenced by onset of walking past 18 months in nine patients; three of these patients were never able to walk independently. One patient each died at ages 1, 3, 4, and 8 years; all others have survived to present (mean age, 13 years). The mean curve of the patients' spines at presentation was 38 degrees. Eleven curves were double major, two were thoracolumbar, and one was double thoracic. Brace wear did not halt curve progression in any of the nine patients for whom it was used. Instrumentation without fusion was used in three patients for a mean of 3 years, with best results in one nonkyphotic curve. Nine patients underwent instrumented fusion at a mean age of 6.6 years (range, 3-13 years). Mean curve correction was 51% (from 72 degrees to 34 degrees). Final mean curve was 54 degrees for a mean correction of 20% at the 5-year (average, 5.4 years) follow-up examination. Acute complications occurred in three patients, and five patients needed a second surgery for late complications. Causes for curve increase after surgery included growth and loss of fixation. In this most severe form of Marfan syndrome, bracing has a limited role and is only to be used if the curve is less than 40 degrees. Surgery should not be performed on a patient younger than four years of age because many patients with large curves before this age will succumb spontaneously to cardiac complications. Instrumentation without fusion should be considered only for patients with no significant kyphosis. Results of fusion are better for patients who are older than five years of age.

Marfan's syndrome: a family affair

Marfan's syndrome (MFS), a heritable connective tissue disorder, may result in cardiac valvular insufficiency, aortic aneurysm or dissection, dislocated lens, and musculoskeletal abnormalities. During a 20-month period (1994-96), an interdisciplinary health care team at a central Virginia medical center evaluated the histories of 112 persons from 15 different families for the presence of MFS-related traits. Seventy-five had at least one MFS-related trait, and 27 subjects underwent echocardiography to evaluate for aortic root dilatation and valvular lesions. Forty-three patients (57.3%) in the above cohort demonstrated significant cardiovascular lesions, with 20 undergoing cardiac surgery. Thirty-one patients (41.3%) were initially seen with significant ocular lesions, and 38 (50.7%) displayed orthopedic deformities. The health care team developed strategies for long-term management of persons with MFS, including antihypertensive therapy, periodic testing, risk-factor modification, genetic counseling, and surgery for appropriate patients. Proactive, consistent management of MFS families will improve long-term health outcomes for this patient population.

The PKD1 gene produces a developmentally regulated protein in mesenchyme and vasculature

Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common human genetic diseases. In addition to polycystic kidneys, the disease can cause cystic changes in liver and other organs, cardiac valvular insufficiency and cerebral arterial aneurysms. Using antibodies raised against the predicted gene product of PKD1, which is mutated in about 85% of ADPKD cases, we show that PKD1 is a 530-kD protein localized to the extracellular matrix of kidney, liver and cerebral blood vessels. We discovered that the PKD1 protein was highly expressed in the mesenchyme of developing kidney and liver, transiently localized in the developing glomerulus and juxtaglomerular apparatus and restricted to perivascular, extraglomerular areas in adult renal cortex. These data suggest that the PKD1 protein plays a role in renal and hepatic morphogenesis.

Congenital Partial and Complete Absence of the Pericardium

Between 1952 and 1991, 15 Mayo patients were found to have partial or complete absence of the pericardium at the time of a cardiovascular surgical procedure. One patient with complete absence of the left pericardium had symptoms possibly related to the pericardial abnormality. This 42-year-old man had severe insufficiency of the tricuspid valve attributable to chordal rupture of the anterior leaflet, possibly precipitated by complete displacement of the heart into the left pleural space. Excision of the ruptured chordae and plication of the anterior flail leaflet rendered a competent tricuspid valve. In two patients, a small defect in the pericardium was repaired. Three patients who underwent operation for complex congenital heart disease died: two early postoperatively and one late after a reoperation. In the other 12 patients, no early or late postoperative complications were encountered. Although rare and usually asymptomatic, complete and partial deficiency of the pericardium may lead to serious complications such as cardiac valvular insufficiency or incarceration of cardiac tissue.