Nanoparticle Delivery of STAT3 Alleviates Pulmonary Hypertension in a Mouse Model of Alveolar Capillary Dysplasia.

BACKGROUND: Pulmonary hypertension (PH) is a common complication in patients with alveolar capillary dysplasia with misalignment of pulmonary veins (ACDMPV), a severe congenital disorder associated with mutations in the FOXF1 gene. Although the loss of alveolar microvasculature causes PH in patients with ACDMPV, it is unknown whether increasing neonatal lung angiogenesis could prevent PH and right ventricular (RV) hypertrophy. METHODS: We used echocardiography, RV catheterization, immunostaining, and biochemical methods to examine lung and heart remodeling and RV output in Foxf1WT/S52F mice carrying the S52F Foxf1 mutation (identified in patients with ACDMPV). The ability of Foxf1WT/S52F mutant embryonic stem cells to differentiate into respiratory cell lineages in vivo was examined using blastocyst complementation. Intravascular delivery of nanoparticles with a nonintegrating Stat3 expression vector was used to improve neonatal pulmonary angiogenesis in Foxf1WT/S52F mice and determine its effects on PH and RV hypertrophy. RESULTS: Foxf1WT/S52F mice developed PH and RV hypertrophy after birth. The severity of PH in Foxf1WT/S52F mice directly correlated with mortality, low body weight, pulmonary artery muscularization, and increased collagen deposition in the lung tissue. Increased fibrotic remodeling was found in human ACDMPV lungs. Mouse embryonic stem cells carrying the S52F Foxf1 mutation were used to produce chimeras through blastocyst complementation and to demonstrate that Foxf1WT/S52F embryonic stem cells have a propensity to differentiate into pulmonary myofibroblasts. Intravascular delivery of nanoparticles carrying Stat3 cDNA protected Foxf1WT/S52F mice from RV hypertrophy and PH, improved survival, and decreased fibrotic lung remodeling. CONCLUSIONS: Nanoparticle therapies increasing neonatal pulmonary angiogenesis may be considered to prevent PH in ACDMPV.

Cardiopulmonary Testing before Pediatric Adenotonsillectomy for Severe and Very Severe Obstructive Sleep Apnea Syndrome.

OBJECTIVES/HYPOTHESIS: Adenotonsillectomy is first-line treatment for pediatric obstructive sleep apnea syndrome (OSAS) when not otherwise contraindicated. There is concern severe OSAS increases risk of comorbid cardiopulmonary abnormalities, such as ventricular hypertrophy or pulmonary hypertension, which preoperative testing could detect. Our objective is to determine if there is a severity of pediatric OSAS where previously undetected cardiopulmonary comorbidities are likely. STUDY DESIGN: Retrospective chart review. METHODS: We performed a retrospective review of 358 patients ≤21 years with severe OSAS who underwent adenotonsillectomy at a tertiary hospital June 1, 2016 to June 1, 2018. We extracted demographics, comorbidities, polysomnography, and preoperative tests. Wilcoxon rank-sum and logistic regression estimated associations of OSAS severity (based on obstructive apnea-hypopnea index [OAHI], hypoxia, hypercarbia) with preoperative echocardiograms and chest X-rays (CXRs). RESULTS: Mean age was 5.9 (±3.6) years and 52% were male. Mean OAHI and oxygen saturation nadir were 30.3 (±23.8) and 80.7% (±9.2), respectively. OAHI ≥60 was associated with having a preoperative echocardiogram (OR, 3.8; 95% CI, 1.7-8.5) or CXR (OR, 3.0; 95% CI, 1.4-6.8) compared to OAHI 10-59. There were no significant associations between OSAS severity and test abnormalities. The presence of previously diagnosed cardiopulmonary comorbidities was associated with abnormalities on echocardiogram (OR, 36; 95% CI, 4.1-320.1) and CXR (OR, 4.1; 95% CI, 1.2-14.4). CONCLUSIONS: Although pediatric patients with very severe OSAS (OAHI ≥60) underwent more pre-adenotonsillectomy cardiopulmonary tests, OSAS severity did not predict abnormal findings. Known cardiopulmonary comorbidities may be a better indication for cardiopulmonary testing than polysomnographic parameters, which could streamline pre-adenotonsillectomy evaluation and reduce cost. LEVEL OF EVIDENCE: 4 Laryngoscope, 131:2361-2368, 2021.

Right Ventricular Hypertrophy and Dilation in Patients With Human Immunodeficiency Virus in the Absence of Clinical or Echocardiographic Pulmonary Hypertension.

BACKGROUND: Involvement of right-sided heart chambers (RSHCs) in patients infected with human immunodeficiency virus (HIV) is common and is usually attributed to pulmonary arterial or venous hypertension (PH). However, myocardial involvement in patients with HIV is also common and might affect RSHCs even in the absence of overt PH. Our aim was to define morphologic and functional alterations in RSHC in patients with HIV and without PH. METHODS AND RESULTS: A total of 50 asymptomatic patients with HIV and 25 control subjects without clinical or echocardiographic signs for PH were included in the study. Transthoracic echocardiography was used to obtain measurements. Patients with HIV had significantly increased right ventricular end-diastolic diameter (RVEDD) and right ventricular free wall thickness (RVFWT), as well as increased right atrial area and pulmonary arterial diameter, compared with control subjects. After adjustment for age, sex, and body surface area, RVFWT (average 1.81 mm, 95% confidence interval [CI] 0.35-3.26 mm) and RVEDD (average 6.82 mm, 95% CI 2.40-11.24 mm) were significantly higher in subjects infected with HIV. More patients with right ventricular hypertrophy were on antiretroviral treatment, and RVFWT was on average 1.3 mm higher (95% CI 0.24-2.37 mm) in patients on antiretroviral treatment after adjustment for confounders. CONCLUSIONS: These findings suggest that alterations in RSHCs were present in patients with HIV without PH.

[Clinical and electrocardiographic aspect of pulmonary embolism masking aortic dissection revealed by thoracic CT angiography]. / Aspect clinico-électrocardiographique d'embolie pulmonaire masquant une dissection aortique révélé par l'angioscanner thoracique.

We here report the case of a 52-year old hypertensive, obese woman (BMI 32,46 kg/m2) with a past history of smoking and without evidence-based risk factors of venous thromboembolism, hospitalized for left chest pain radiating to the dorsolumbar region associated with dyspnoea. Clinical examination on hopitalization showed left blood pressure 100/60 mmHg, tachycardia 100/min, oxygen desaturation index at 88% with the patient breathing ambient air, normal cardiopulmonary auscultation, peripheral pulses palpable and no symptoms of phlebitis of the lower limbs. The ECG showed right axis deviation, S1Q3 pattern, right ventricular hypertrophy and right bundle branch block (A, B, C). The patient underwent emergency thoracic CT angiography objectifying aortic dissection from the origin of the aorta to the iliac bifurcation (Stanford A). Our patient received medical care based on blood pressure and heart rate control as well as on analgesics, with good evolution in the absence of surgical means.

ECG Of The Month: Mental Disturbance for 4 days.

A family brought their 61-year-old mother to the emergency department because for 4 days she had been confused, incoherent, and somnolent. She also had dysphagia, dysarthria, diplopia, and had fallen out of bed. She had been in the hospital 3 weeks earlier for atrial fibrillation and an exacerbation of congestive heart failure. She also carried a diagnosis of chronic obstructive pulmonary disease and used an albuterol inhaler. She was obese (BMI of 45); and had adult-onset diabetes mellitus. She had a 43 pack-year history of cigarette smoking but had recently quit. Soon after arriving in the emergency department, she had an ECG (Figure);.

Delayed recovery of right ventricular systolic function after repair of long-standing tricuspid regurgitation associated with severe right ventricular failure.

After tricuspid valve surgery for long-standing tricuspid regurgitation associated with right ventricular failure, reverse remodelling of the enlarged right ventricle, including recovery of right ventricular systolic function, is unpredictable. We present the case of a 31-year old man with early reduction of dilated right ventricular dimensions and delayed recovery of impaired right ventricular systolic function after valve repair for traumatic tricuspid regurgitation lasting 16 years.

High Arrhythmic Burden but Low Mortality during Long-term Follow-up in Arrhythmogenic Right Ventricular Cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is associated with a high incidence of ventricular tachyarrhythmia and sudden death. The mainstay of management is the implantable cardioverter defibrillator (ICD). A small number of patient cohorts have generated a large number of reports. METHODS: Prospective registry data supplemented with clinical and ICD records of 30 patients with ARVC fulfilling the 2010 modified Task Force Criteria. This cohort has not been reported on previously. RESULTS: Median age at diagnosis: 46yrs (range 21-68); 20 (80%) male; six (19%) Maori. Duration of follow-up: 7.4yrs (range 1.7-23). Implantable cardioverter defibrillator implantation in 26; three (12%) for resuscitated sudden cardiac death; 17 (65%) for symptomatic ventricular tachyarrhythmia; three (12%) for syncope; and three (12%) for family history of sudden death attributable to ARVC. Two patients died during follow-up, one had an ICD, though died of a carcinoma. Thirteen (50%) experienced appropriate ICD therapy with median time to therapy 12 months, and four (15%) experienced inappropriate shock therapy. Male gender was an independent predictor of appropriate ICD therapy (HR 1.6, 95% CI 1.5-2.7, P=0.01). CONCLUSIONS: The long-term prognosis of patients with ARVC is favourable although high proportions receive appropriate ICD therapy. Male gender is an independent predictor of appropriate ICD therapy.

Como conduzir pacientes assintomáticoscom extrassístoles ventriculares? / How to approach asymptomatic patients with premature ventricular contractions?

As extrassístoles ventriculares (EV) são conhecidas desde o século VII AC, e até o momento existem dúvidas pelos clínicos e mesmo entre grande número de cardiologistas,sobre como abordá-las e consequente terapêutica. Nas últimas décadas surgiram evidências relatadas em trabalhos com grande número de pacientes e em diretrizes devárias sociedades de que as EV em indivíduos sem cardiopatia estrutural, após avaliaçãopor métodos diagnósticos disponíveis, não necessitam de maiores preocupações, já queos riscos de morte se equivalem a uma população normal ou mesmo aos coronarianos com lesões arteriais discretas. Isso equivale a dizer, os assintomáticos não necessitam de nenhum tratamento específico, e se apresentarem sintomas decorrentes da arritmia, apenas terapia com β-bloqueadores e aconselhamento médico. Porém, assintomáticos portadoresde EV com possibilidades de desenvolver quadros clínicos mais severos, devem ter uma abordagem mais criteriosa. Assim, devem submeter-se a avaliação clínica detalhada e talvez emprego de terapia específica, com medicamentos antiarrítmicos e até ablação por cateter, portadores de EV assintomáticos quanto à arritmia, quando esta for frequente– acima de 500 EV por hora – com cardiopatia estrutural, eletrocardiograma com evidênciasde alterações eletrogenéticas, miocardiopatia dilatada e hipertrófica, possibilidade de indução de arritmias ventriculares malignas e fração de ejeção em fase de deterioração...

Premature ventricular contractions (PVC) were first described in the 7th Century BC,but until now, there are doubts among medical professionals, and even among many cardiologists, as to how to address them, or the best conduct for their treatment. In recente decades, evidence has emerged from large clinical trials, and the guidelines of various societies, that PVC in individuals without structural heart disease, after evaluation by the available diagnostic methods, are not a cause for major concern, as the risk of death is equivalent to that of the normal population, or even coronary patients with mild arterial lesions.This means that asymptomatic patients do not require any specific treatment, and if they present symptoms resulting from the arrhythmia, therapy with β-blockers alone, and medical guidance, are advised. However, asymptomatic patients with PVC with the possibility of developing more severe clinical conditions should be more carefully investigated.Patients with asymptomatic PVC in terms of arrhythmia should therefore be submitted to adetailed clinical evaluation, possibly with specific therapy, with antiarrhythmic medications and even catheter ablation, in cases where the arrhythmia is frequent – above 500 PVC per hour – with structural heart disease, electrocardiogram with evidence of electrogenetic alterations, dilated and hypertrophic myocardiopathy, possibility of induction of malignant ventricular arrhythmias, and ejection fraction in the deterioration phase...

Pathogenic structural heart changes in early tricuspid regurgitation.

OBJECTIVE: Severe, late functional tricuspid regurgitation is characterized by annulus dilation, right ventricular enlargement, and papillary muscle displacement with leaflet tethering. However, the early stages of mild tricuspid regurgitation and its progression are poorly understood. This study examined structural heart changes in mild, early tricuspid regurgitation. METHODS: Sequential patients undergoing cardiac computed tomography and transthoracic echocardiography with tricuspid regurgitation were identified and evaluated. The tricuspid annulus area and chamber volumes were measured by computed tomography angiography and categorized by tricuspid regurgitation severity. RESULTS: Patients (n = 622) were divided into 3 groups by tricuspid regurgitation severity: no/trace (n = 386), mild (n = 178), and moderate/severe tricuspid regurgitation (n = 58). Annulus area was highly dependent on and proportional to regurgitation severity and correlated with both right/left atrial enlargement. Annulus area most strongly correlated with right and left atrial volume, and the annulus shape changed from elliptical to circular in moderate/severe tricuspid regurgitation. Mild tricuspid regurgitation was associated with less right/left atrial enlargement than significant tricuspid regurgitation, normal right ventricular size, and annular dilation. Significant tricuspid regurgitation was associated with annular dilation, circularization, and right ventricular enlargement. Mild and significant tricuspid regurgitation were differentiated by annulus area and indexed right ventricular volume. CONCLUSIONS: Tricuspid annular dilation and right/left atrial enlargement comprise early events in mild functional tricuspid regurgitation. Atrial enlargement occurs before right ventricular dilation, which occurs late, when tricuspid regurgitation is severe. Atrial volume and tricuspid annular dilation are early and sensitive indicators of tricuspid regurgitation significance.

Sleep disordered breathing and enlargement of the right heart after myocardial infarction.

Structural and functional integrity of the right heart is important in the prognosis after acute myocardial infarction (AMI). The objective of this study was to assess the impact of sleep disordered breathing (SDB) on structure and function of the right heart early after AMI. 54 patients underwent cardiovascular magnetic resonance 3-5 days and 12 weeks after AMI, and were stratified according to the presence of SDB, defined as an apnoea-hypopnoea index of ≥ 15 events · h(-1). 12 weeks after AMI, end-diastolic volume of the right ventricle had increased significantly in patients with SDB (n=27) versus those without (n=25) (mean ± sd 14 ± 23% versus 0 ± 17%, p=0.020). Multivariable linear regression analysis accounting for age, sex, body mass index, smoking, left ventricular mass and left ventricular end-systolic volume showed that the apnoea-hypopnoea index was significantly associated with right ventricular end-diastolic volume (B-coefficient 0.315 (95% CI 0.013-0.617); p=0.041). From baseline to 12 weeks, right atrial diastolic area increased more in patients with SDB (2.9 ± 3.7 cm(2) versus 1.0 ± 2.4 cm(2), p=0.038; when adjusted for left ventricular end systolic volume, p=0.166). SDB diagnosed shortly after AMI predicts an increase of right ventricular end-diastolic volume and possibly right atrial area within the following 12 weeks. Thus, SDB may contribute to enlargement of the right heart after AMI.

Effect of the 2010 task force criteria on reclassification of cardiovascular magnetic resonance criteria for arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: We sought to evaluate the effect of application of the revised 2010 Task Force Criteria (TFC) on the prevalence of major and minor Cardiovascular Magnetic Resonance (CMR) criteria for Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) versus application of the original 1994 TFC. We also assessed the utility of MRI to identify alternative diagnoses for patients referred for ARVC evaluation. METHODS: 968 consecutive patients referred to our institution for CMR with clinical suspicion of ARVC from 1995 to 2010, were evaluated for the presence of major and minor CMR criteria per the 1994 and 2010 ARVC TFC. CMR criteria included right ventricle (RV) dilatation, reduced RV ejection fraction, RV aneurysm, or regional RV wall motion abnormalities. When quantitative measures of RV size and function were not available, and in whom abnormal size or function was reported, a repeat quantitative analysis by 2 qualified CMR physicians in consensus. RESULTS: Of 968 patients, 220 (22.7%) fulfilled either a major or a minor 1994 TFC, and 25 (2.6%) fulfilled any of the 2010 TFC criterion. Among patients meeting any 1994 criteria, only 25 (11.4%) met at least one 2010 criterion. All patients who fulfilled a 2010 criteria also satisfied at least one 1994 criterion. Per the 2010 TFC, 21 (2.2%) patients met major criteria and 4 (0.4%) patients fulfilled at least one minor criterion. Eight patients meeting 1994 minor criteria were reclassified as satisfying 2010 major criteria, while 4 patients fulfilling 1994 major criteria were reclassified to only minor or no criteria under the 2010 TFC.Eighty-nine (9.2%) patients had alternative cardiac diagnoses, including 43 (4.4%) with clinically significant potential ARVC mimics. These included cardiac sarcoidosis, RV volume overload conditions, and other cardiomyopathies. CONCLUSIONS: Application of the 2010 TFC resulted in reduction of total patients meeting any diagnostic CMR criteria for ARVC from 22.7% to 2.6% versus the 1994 TFC. CMR identified alternative cardiac diagnoses in 9.2% of patients, and 4.4% of the diagnoses were potential mimics of ARVC.

Does limited right ventriculotomy prevent right ventricular dilatation and dysfunction in patients who undergo transannular repair of tetralogy of Fallot? Matched comparison of magnetic resonance imaging parameters with conventional right ventriculotomy long-term after repair.

OBJECTIVE: The objective of this study was to test the hypothesis that limited (<1 cm) right ventriculotomy (RV-tomy) in the setting of transannular tetralogy of Fallot (TOF) repair might result in less right ventricular (RV) dilatation and dysfunction compared with conventional RV-tomy. METHODS: Between June 2002 and April 2012, 113 patients with transannular repair of TOF underwent magnetic resonance imaging (MRI). Patients were divided into a limited RV-tomy group (n = 39) and a conventional RV-tomy group (n = 74). Thirty-nine patients from each group were matched for comparison using propensity scores. The MRI parameters of the 2 groups were compared. RESULTS: The interval between TOF repair and MRI examination was shorter in the limited RV-tomy group (limited, 12.7 ± 3.8 years; conventional, 17.2 ± 4.7 years; P < .001). Indexed RV volumes were similar between the groups (RV end-diastolic volume index: 149 ± 31 mL/m(2) vs 152 ± 42 mL/m(2); P = .704. RV end-systolic volume index: 70 ± 24 mL/m(2) vs 77 ± 38 mL/m(2); P = .313). There was no difference in the RV ejection fraction between the groups (54% ± 9% vs 51% ± 9%; P = .160). Propensity score-matched comparison also revealed no differences in RV volume and function. CONCLUSIONS: No long-term benefits of limited RV-tomy were demonstrated compared with conventional RV-tomy in patients who underwent transannular TOF repair, at least in terms of RV volume and function. Further studies are necessary to define the role of limited RV-tomy in patients who undergo transannular TOF repair.

The importance of trabecular hypertrophy in right ventricular adaptation to chronic pressure overload.

To assess the contribution of right ventricular (RV) trabeculae and papillary muscles (TPM) to RV mass and volumes in controls and patients with pulmonary arterial hypertension (PAH). Furthermore, to evaluate whether TPM shows a similar response as the RV free wall (RVFW) to changes in pulmonary artery pressure (PAP) during follow-up. 50 patients underwent cardiac magnetic resonance (CMR) and right heart catheterization at baseline and after one-year follow-up. Furthermore 20 controls underwent CMR. RV masses were assessed with and without TPM. TPM constituted a larger proportion of total RV mass and RV end-diastolic volume (RVEDV) in PAH than in controls (Mass: 35 ± 7 vs. 25 ± 5 %; p < 0.001; RVEDV: 17 ± 6 vs. 12 ± 6 %; p = 0.003). TPM mass was related to the RVFW mass in patients (baseline: R = 0.65; p < 0.001; follow-up: R = 0.80; p < 0.001) and controls (R = 0.76; p < 0.001). In PAH and controls, exclusion of TPM from the assessment resulted in altered RV mass, volumes and function than when included (all p < 0.01). Changes in RV TPM mass (ß = 0.44; p = 0.004) but not the changes in RVFW mass (p = 0.095) were independently related to changes in PAP during follow-up. RV TPM showed a larger contribution to total RV mass in PAH (~35 %) compared to controls (~25 %). Inclusion of TPM in the analyses significantly influenced the magnitude of the RV volumes and mass. Furthermore, TPM mass was stronger related to changes in PAP than RVFW mass. Our results implicate that TPM are important contributors to RV adaptation during pressure overload and cannot be neglected from the RV assessment.

Validity of the surface electrocardiogram criteria for right ventricular hypertrophy: the MESA-RV Study (Multi-Ethnic Study of Atherosclerosis-Right Ventricle).

OBJECTIVES: The study aimed to assess the diagnostic properties of electrocardiographic (ECG) criteria for right ventricular hypertrophy (RVH) measured by cardiac magnetic resonance imaging (cMRI) in adults without clinical cardiovascular disease. BACKGROUND: Current ECG criteria for RVH were based on cadaveric dissection in small studies. METHODS: MESA (Multi-Ethnic Study of Atherosclerosis) performed cMRIs with complete right ventricle (RV) interpretation on 4,062 participants without clinical cardiovascular disease. Endocardial margins of the RV were manually contoured on diastolic and systolic images. The ECG screening criteria for RVH from the 2009 American Heart Association Recommendations for Standardization and Interpretation of the ECG were examined in participants with and without left ventricular (LV) hypertrophy or reduced ejection fraction. RVH was defined using sex-specific normative equations based on age, height, and weight. RESULTS: The study sample with normal LV morphology and function (n = 3,719) was age 61.3 ± 10.0 years, 53.5% female, 39.6% Caucasian, 25.5% African American, 21.9% Hispanic, and 13.0% Asian. The mean body mass index was 27.9 ± 5.0 kg/m(2). A total of 6% had RVH, which was generally mild. Traditional ECG criteria were specific (many >95%) but had low sensitivity for RVH by cMRI. The positive predictive values were not sufficiently high as to be clinically useful (maximum 12%). The results did not differ based on age, sex, race, or smoking status, or with the inclusion of participants with abnormal LV mass or function. Classification and regression tree analysis revealed that no combination of ECG variables was better than the criteria used singly. CONCLUSIONS: The recommended ECG screening criteria for RVH are not sufficiently sensitive or specific for screening for mild RVH in adults without clinical cardiovascular disease.

Role of myocardial hypertrophy on acute and chronic right ventricular performance in relation to chronic volume overload in a porcine model: relevance for the surgical management of tetralogy of Fallot.

OBJECTIVES: The age for correction of tetralogy of Fallot has progressively declined to the postnatal period, often despite an increased rate of transannular patch repair. However, the long-term effect of premature exposure to chronic pulmonary insufficiency on the right ventricle remains unknown. On the basis of the relationship between the duration of pressure overload and age, the role of previous pressure load-related hypertrophy on right ventricular (RV) performance after chronic volume overload was investigated in a porcine model. METHODS: RV hypertrophy (RVH), induced by pulmonary artery banding, was studied in pigs with (RVH plus pulmonary insufficiency [PI]) and without (RVH) subsequent PI. The effect of volume overload was compared between these 2 groups and pigs without RVH but with PI and controls (sham). Both acute and chronic effects on RV function were studied using conductance technology and validated using echocardiography. RESULTS: After chronic volume overload, the end-systolic and end-diastolic volumes were smaller in the RVH+PI group than in the PI group, including a lower pulmonary regurgitation fraction (25% ± 5% vs 35% ± 5%; P = .002). RVH resulted in better preserved systolic function, confirmed by an increased preload recruitable stroke work slope (14.7 ± 1.8 vs 9.3 ± 1.3 Mw.s/mL; P = .025) and higher RV ejection fraction (51% ± 3% vs 45% ± 4%; P = .05). Myocardial stiffness was impaired in the RVH+PI group versus the PI group (ß, 0.19 ± 0.03 vs 0.12 ± 0.02 mL(-1); P = .001), presenting restrictive physiology only in the condition associating RVH and PI. CONCLUSIONS: The results of the present study have demonstrated that RVH attenuates the RV remodeling process related to chronic PI. It enables better preservation of contractility but at the cost of sustained diastolic impairment. These findings might help to determine the timing and strategy for repair of tetralogy of Fallot when RV outflow tract morphology indicates a definite need for transannular reconstruction.