The influence of Marfans and bicuspid valves on outcomes following aortic valve reimplantation.

BACKGROUND: We analyzed our early and midterm results with aortic valve reimplantation surgery to determine the influence of Marfan syndrome and bicuspid valves on outcomes with this technique. METHODS: Between March 2004 and December 2015, 267 patients underwent aortic valve reimplantation operations. The mean diameter of the sinuses of Valsalva was 50 ± 3 mm and moderate/severe aortic regurgitation was present in 34.4% of these patients. A bicuspid aortic valve was present in 21% and 40% had Marfan syndrome. RESULTS: Overall 30-day mortality was 0.37% (1/267). Mean follow-up was 59.7 ± 38.7 months. Overall survival at 1, 3, and 5 years was 98 ± 8%, 98 ± 1%, and 94 ± 2%, respectively. Freedom from reoperation and aortic regurgitation >II was 99 ± 5%, 98 ± 8%, 96.7 ± 8%, and 99 ± 6%, 98 ± 1%, 98 ± 1%, respectively at 1, 3, and 5 years follow-up, with no differences between Marfan and bicuspid aortic valve groups. (p = 0.94 and p = 0.96, respectively). No endocarditis or thromboembolic complications were documented, and 93.6% of the patients did not receive any anticoagulation therapy. CONCLUSIONS: The reimplantation technique for aortic root aneurysms is associated with excellent clinical and functional outcomes at short and mid-term follow-up.

Changes in echocardiographic parameters over time in paradoxical low-flow low-gradient aortic stenosis.

AIMS: To assess the progression of the disease and evolution of the main echocardiographic variables for quantifying AS in patients with severe low-flow low-gradient (LFLG) AS compared to other severe AS subtypes. METHODS AND RESULTS: Longitudinal, observational, multicenter study including consecutive asymptomatic patients with severe AS (aortic valve area, AVA < 1.0 cm²) and normal left ventricle ejection fraction (LVEF ≥ 50%). Patients were classified according to baseline echocardiography into: HG (high gradient; mean gradient ≥ 40 mmHg), NFLG (normal-flow low-gradient; mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35mL/m2), or LFLG (mean gradient < 40 mmHg, SVi ≤ 35 mL/m²). AS progression was analyzed by comparing patients' baseline measurements and their last follow-up measurements or those taken prior to aortic valve replacement (AVR). Of the 903 included patients, 401 (44.4%) were HG, 405 (44.9%) NFLG, and 97 (10.7%) LFLG. Progression of the mean gradient in a linear mixed regression model was greater in low-gradient groups: LFLG vs. HG (regression coefficient 0.124, P = 0.005) and NFLG vs. HG (regression coefficient 0.068, P = 0.018). No differences were observed between the LFLG and NFLG groups (regression coefficient 0.056, P = 0.195). However, AVA reduction was slower in the LFLG group compared to the NFLG (P < 0.001). During follow-up, in conservatively-managed patients, 19.1% (n = 9) of LFLG patients evolved to having NFLG AS and 44.7% (n = 21) to having HG AS. In patients undergoing AVR, 58.0% (n = 29) of LFLG baseline patients received AVR with a HG AS. CONCLUSION: LFLG AS shows an intermediate AVA and gradient progression compared to NFLG and HG AS. The majority of patients initially classified as having LFLG AS changed over time to having other severe forms of AS, and most of them received AVR with a HG AS.

Acute Post-Traumatic Aortic Regurgitation.

A 16-year-old girl with a history of blunt chest trauma was admitted because of heart failure symptoms. Transthoracic echocardiography showed severe eccentric aortic regurgitation. Cardiac computed tomography revealed a pseudoaneurysm of the right sinus of Valsalva. We present a rare clinical presentation of a life-threatening condition. (Level of Difficulty: Intermediate.).

Aortic events in pregnant patients with Marfan syndrome. Lessons from a multicenter study.

INTRODUCTION AND OBJECTIVES: Pregnancy in women with Marfan syndrome (MS) is associated with an increased risk of aortic events. The clinical evidence on pregnant patients with MS is limited and there is no specific consensus on their optimal management. We report our multicenter experience. METHODS: From January 2004 to January 2020, 632 patients with MS underwent periodic monitoring in Marfan units. During this period, we identified all pregnant women with MS and analyzed the incidence of aortic events during pregnancy and puerperium. RESULTS: There were 133 pregnancies in 89 women with MS (8 women with prior aortic surgery). There were no maternal deaths, but 5 women had aortic events during the third trimester and puerperium (type A dissections in 2, type B dissection in 1, and significant [≥ 3mm] aortic growth in 2). The aortic event rate was 3.7%. Pregestational aortic diameter≥ 40mm showed a nonsignificant association with aortic events (P=.058). Fetal mortality was 3% and 37.6% of births were cesarean deliveries. CONCLUSIONS: Women with MS have an increased risk of aortic events during pregnancy, especially in the third trimester and postpartum period. Patients with MS and aortic diameters ≥40mm should be assessed in experienced centers for prophylactic aortic surgery before pregnancy. It is important to provide early diagnosis, prepregnancy study of the aorta, beta-blocker administration, and close monitoring during pregnancy, especially during the last trimester and postpartum.

Aortic valve reimplantation in patients with connective tissue syndromes: A 15-year follow-up.

OBJECTIVES: The goal of this study was to analyse early- and long-term outcomes of aortic valve reimplantation (David operation) in patients with heritable thoracic aortic disease. METHODS: This is a retrospective observational analysis using data from a prospectively maintained surgical database from March 2004 to April 2021. Patients with heritable thoracic aortic disease were included in the study. RESULTS: A total of 157 patients with aortic root aneurysm with the diagnosis of heritable thoracic aortic disease received the David procedure. Marfan syndrome was found in 143 (91.1%) patients, Loeys-Dietz in 13 and Ehler-Danlos in 1 patient. The median age was 35.0 (IQR: 17.5) years and the median ascending aorta diameter in the Valsalva sinuses was 48 mm (IQR: 4). A Valsalva graft was used in 8 patients; the David V technique was performed in the rest of the cases. The median follow-up time was 7.3 years [standard deviation: 0.58, 95% confidence interval (CI): 6.12-8.05]. Only 2 patients died during the follow-up period. The overall survival was 99% (95% CI: 95%; 99%); 98% (95% CI: 92%; 99%); and 98% (95% CI: 92%; 99%) at 5, 10 and 15 years. Freedom from significant aortic regurgitation (AR> II), reintervention and postoperative type-B dissection was 90% (95% CI: 77%; 95%), 96% (95% CI: 91%; 99%) and 87% (95% CI: 68%; 95%) at 15 years, respectively. No differences were found in any outcome between Marfan syndrome and Loeys-Dietz syndrome. No statistically significant differences in survival were found when we compared expected gender- and age-specific population survival values. CONCLUSIONS: The David operation is an excellent option for the treatment of patients with heritable thoracic aortic disease and dilatated aortic root. Surgical expertise in referral centres is essential to achieve the best long-term results.

Prognosis of Paradoxical Low-Flow Low-Gradient Aortic Stenosis: A Severe, Non-critical Form, With Surgical Treatment Benefits.

Objectives: To determine the risk of mortality and need for aortic valve replacement (AVR) in patients with low-flow low-gradient (LFLG) aortic stenosis (AS). Methods: A longitudinal multicentre study including consecutive patients with severe AS (aortic valve area [AVA] < 1.0 cm2) and normal left ventricular ejection fraction (LVEF). Patients were classified as: high-gradient (HG, mean gradient ≥ 40 mmHg), normal-flow low-gradient (NFLG, mean gradient < 40 mmHg, indexed systolic volume (SVi) > 35 ml/m2) and LFLG (mean gradient < 40 mmHg, SVi ≤ 35 ml/m2). Results: Of 1,391 patients, 147 (10.5%) had LFLG, 752 (54.1%) HG, and 492 (35.4%) NFLG. Echocardiographic parameters of the LFLG group showed similar AVA to the HG group but with less severity in the dimensionless index, calcification, and hypertrophy. The HG group required AVR earlier than NFLG (p < 0.001) and LFLG (p < 0.001), with no differences between LFLG and NFLG groups (p = 0.358). Overall mortality was 27.7% (CI 95% 25.3-30.1) with no differences among groups (p = 0.319). The impact of AVR in terms of overall mortality reduction was observed the most in patients with HG (hazard ratio [HR]: 0.17; 95% CI: 0.12-0.23; p < 0.001), followed by patients with LFLG (HR: 0.25; 95% CI: 0.13-0.49; p < 0.001), and finally patients with NFLG (HR: 0.29; 95% CI: 0.20-0.44; p < 0.001), with a risk reduction of 84, 75, and 71%, respectively. Conclusions: Paradoxical LFLG AS affects 10.5% of severe AS, and has a lower need for AVR than the HG group and similar to the NFLG group, with no differences in mortality. AVR had a lower impact on LFLG AS compared with HG AS. Therefore, the findings of the present study showed LFLG AS to have an intermediate clinical risk profile between the HG and NFHG groups.

Aortic disease in Marfan syndrome is caused by overactivation of sGC-PRKG signaling by NO.

Thoracic aortic aneurysm, as occurs in Marfan syndrome, is generally asymptomatic until dissection or rupture, requiring surgical intervention as the only available treatment. Here, we show that nitric oxide (NO) signaling dysregulates actin cytoskeleton dynamics in Marfan Syndrome smooth muscle cells and that NO-donors induce Marfan-like aortopathy in wild-type mice, indicating that a marked increase in NO suffices to induce aortopathy. Levels of nitrated proteins are higher in plasma from Marfan patients and mice and in aortic tissue from Marfan mice than in control samples, indicating elevated circulating and tissue NO. Soluble guanylate cyclase and cGMP-dependent protein kinase are both activated in Marfan patients and mice and in wild-type mice treated with NO-donors, as shown by increased plasma cGMP and pVASP-S239 staining in aortic tissue. Marfan aortopathy in mice is reverted by pharmacological inhibition of soluble guanylate cyclase and cGMP-dependent protein kinase and lentiviral-mediated Prkg1 silencing. These findings identify potential biomarkers for monitoring Marfan Syndrome in patients and urge evaluation of cGMP-dependent protein kinase and soluble guanylate cyclase as therapeutic targets.

Aortic Complications in Marfan Syndrome: Should We Anticipate Preventive Aortic Root Surgery?

BACKGROUND: The purpose of this study was to analyze the risk of aortic events (death, dissection, or aortic rupture) associated with Marfan syndrome and decide on the optimal timing for preventive surgery on the aortic root. METHODS: From January 2004 to June 2015, 397 patients from Marfan Units were studied by echocardiographic and computed tomography and magnetic resonance imaging of aorta and periodic annual monitoring. Mean follow-up was 5.6 ± 2.7 years. The annual incidence of aortic events was assessed according to aortic diameters for the optimal time for prophylactic surgery to be decided on. RESULTS: Mean age at the first visit was 28.4 ± 14.5 years, with mean sinuses of Valsalva diameter of 37.1 ± 6.6 mm., Eleven aortic events occurred during follow-up: seven deaths and four acute aortic dissections. Mean annual risk of an aortic event was 0.5% (risk of death 0.32% and risk of aortic dissection 0.18%). The increase in aortic diameters was associated with increased risk of 0.2% per year (95% confidence interval [CI], 0.03 to 0.5) with diameters less than 40 mm, 0.3% per year (95% CI, 0.1 to 1.4) between 40 and 44 mm, 1.3% per year (95% CI, 0.3 to 4.6) between 45 and 49 mm, and 5.2% per year (95% CI, 0.4 to 12.4) with diameters 50 mm or greater. Fifty-six patients underwent elective surgery with no inhospital mortality. Overall survival at 3, 5, and 10 years was 99% ± 5%, 98.6% ± 6%, and 95.5% ± 2.5%, respectively. CONCLUSIONS: The incidence of aortic events in patients with Marfan syndrome followed at specific units is low, although the risk increases with aortic diameters of 45 mm or greater. These results support current indications, but we consider it reasonable at experienced centers (elective root aortic surgery mortality less than 1%) to indicate an early surgery when the aortic root exceeds 45 mm.

Immunohistological Analysis of Intracoronary Thrombus Aspirate in STEMI Patients: Clinical Implications of Pathological Findings.

INTRODUCTION AND OBJECTIVES: Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress. METHODS: This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients' clinical and angiographic features, estimation of survival curves, and logistic regression analysis. RESULTS: Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001). CONCLUSIONS: The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection.

Analysis of diagnostic and therapeutic strategies in advanced cardiac light-chain amyloidosis.

BACKGROUND: Prognosis of advanced cardiac light-chain amyloidosis (ACAL) is ominous. Diagnosis of ACAL is frequently preceded by several biopsies of non-clinically affected tissues, which can result in dangerous treatment delays. Combinations of alkylators and steroids have a limited role in its therapy. Definitive efficacy of bortezomib in ACAL is not widely described. In this study we analyze the diagnostic yield of biopsies and compare the effect of bortezomib with other therapeutic strategies in ACAL patients. METHODS: This study is a retrospective analysis of 40 consecutive ACAL patients treated at our hospital (2005 to 2015). For comparison purposes, the cohort was divided into 2 groups: patients treated with bortezomib (n = 23) and those treated with other therapeutic approaches (non-bortezomib, n = 8). RESULTS: Sensitivity of biopsies of non-clinically affected organs was 23%, as compared with 97% for affected organ biopsies (p < 0.0001). The need for >2 biopsies resulted in an average delay in diagnosis of 4.1 months (p = 0.007). Hematologic response was observed in 96% of patients in the bortezomib group compared with 25% in the non-bortezomib group (relative risk = 3.8; 95% confidence interval 1.14 to 12.75; p = 0.0002). Cardiac response criteria were met by 60% of patients in the bortezomib group as compared with none in the non-bortezomib group (p = 0.005). Survival at 6 months and 1 and 2 years for bortezomib patients was 91%, 91% and 73%, as compared with 58%, 15% and 0% for non-bortezomib patients (log rank, p < 0.0001), respectively. CONCLUSION: In our experience, the sensitivity of biopsies from non-affected organs in ACAL is poor and could result in diagnostic delay. Bortezomib was associated with higher hematologic and cardiac response rates as well as survival when compared with other therapies.

[Nonselected use of direct coronary stenting. The DISCO 2 trial]. / Uso amplio de stenting coronaro directo. Estudio DISCO 2.

INTRODUCTION AND OBJECTIVES: Direct coronary stenting yields immediate long-term clinical results similar to those obtained with balloon predilation, with the advantage of lower costs and procedural times. Until now, direct stenting has been attempted only for selected lesions, so that the potential scope of its use in everyday practice remains unknown. The DISCO 2 trial was designed to identify the number and type of lesions that could be safely treated by direct stenting. Patients and method. 1,269 lesions (886 patients) were treated consecutively in 7 different hospitals. Direct stenting was attempted in all cases, except for total chronic occlusions, severe tortuosity or calcification of the vessel, lesions in the sinus ostium, or bifurcated lesions and vessel diameter < 2.4 mm. If the procedure failed, the stent was recovered and the lesion dilated with a balloon before a second attempt at stenting. RESULTS: Direct stenting was attempted in 585 lesions (54.9% of all electively implanted stents and 46.1% of all angioplasties). This was successful in 553 (94.6%) and failed in 32 (5.4%). In 30 of these latter patients a stent was implanted after predilation. Predictors of failure were tortuosity, location in the nonproximal right coronary artery, age > 65 years and type B2 or C lesion. After 6 months of follow-up the total incidence of major adverse cardiovascular events in patients treated with direct stenting was 6.2%, with a target lesion revascularization rate of 4.45%. CONCLUSIONS: In a mostly nonselected sample of coronary lesions, direct stenting was as safe as stenting with predilation. More than half of all elective stenting procedures can be attempted safely without balloon predilation. Greater need for predilation was associated with tortuosity, nonproximal right coronary artery location, older age and lesion complexity (B2, C). The 6-month clinical outcome was excellent, with a low rate of repeat revascularization.

Análisis inmunohistológico del aspirado intracoronario en pacientes con IAMCEST: implicaciones clínicas de los hallazgos anatomopatológicos / Immunohistological analysis of intracoronary thrombus aspirate in STEMI patients: Clinical implications of pathological findings

Introducción y objetivos: La tromboaspiración permite analizar el material intracoronario en pacientes con infarto agudo de miocardio con elevación del segmento ST. Nuestro objetivo fue caracterizar este material mediante inmunohistología y estudiar su posible relación con el pronóstico. Métodos: Cohorte prospectiva de 142 pacientes sometidos a angioplastia primaria con tromboaspiración positiva. El examen histológico del material aspirado incluyó técnicas de inmunohistoquímica para detectar fragmentos de placa. Se estudiaron variables histológicas (antigüedad del trombo, grado de inflamación, presencia de placa), clínicas y angiográficas de los pacientes. Se realizaron análisis de supervivencia y regresión logística. Resultados: De los marcadores histológicos, solo la presencia de placa (el 63% de las muestras) se relacionó con los eventos clínicos. Los factores asociados a la supervivencia libre de eventos a los 5 años fueron: presencia de placa (el 82,2 frente al 66,0%; p = 0,033), tabaquismo (el 82,5 frente al 66,7%; p = 0,036), arteria responsable del infarto (el 83,3% en infartos de circunfleja o coronaria derecha frente al 68,5% de descendente anterior; p = 0,042); flujo angiográfico final (el 80,8% de II-III frente al 30,0% de 0-I; p < 0,001) y fracción de eyección ≥ 35% (el 83,7 frente al 26,7%; p < 0,001). En el análisis multivariable de regresión (Cox) con dichas variables, se identificaron la presencia de placa (HR = 0,37; IC95%, 0,18-0,77; p = 0,008) y la fracción de eyección (HR = 0,92; IC95%, 0,88-0,95; p < 0,001) como predictores independientes de supervivencia libre de eventos. Conclusiones: La presencia de placa de ateroma en el aspirado coronario de los pacientes con infarto de miocardio transmural puede ser un marcador pronóstico independiente, y el análisis inmunohistoquímico con CD68 es un buen método para detectarlo (AU)

Introduction and objectives: Thrombus aspiration allows analysis of intracoronary material in patients with ST-segment elevation myocardial infarction. Our objective was to characterize this material by immunohistology and to study its possible association with patient progress. Methods: This study analyzed a prospective cohort of 142 patients undergoing primary angioplasty with positive coronary aspiration. Histological examination of aspirated samples included immunohistochemistry stains for the detection of plaque fragments. The statistical analysis comprised histological variables (thrombus age, degree of inflammation, presence of plaque), the patients’ clinical and angiographic features, estimation of survival curves, and logistic regression analysis. Results: Among the histological markers, only the presence of plaque (63% of samples) was associated with postinfarction clinical events. Factors associated with 5-year event-free survival were the presence of plaque in the aspirate (82.2% vs 66.0%; P = .033), smoking (82.5% smokers vs 66.7% nonsmokers; P = .036), culprit coronary artery (83.3% circumflex or right coronary artery vs 68.5% anterior descending artery; P = .042), final angiographic flow (80.8% II-III vs 30.0% 0-I; P < .001) and left ventricular ejection fraction ≥ 35% at discharge (83.7% vs 26.7%; P < .001). On multivariable Cox regression analysis with these variables, independent predictors of event-free survival were the presence of plaque (hazard ratio, 0.37; 95%CI, 0.18-0.77; P = .008), and left ventricular ejection fraction (hazard ratio, 0.92; 95%CI, 0.88-0.95; P < .001). Conclusions: The presence of plaque in the coronary aspirate of patients with ST elevation myocardial infarction may be an independent prognostic marker. CD68 immunohistochemical stain is a good method for plaque detection (AU)

Evaluation of a telemedicine service for the secondary prevention of coronary artery disease.

PURPOSE: Efficient ways are needed to implement the secondary prevention (SP) of coronary heart disease. Because few studies have investigated Web-based SP programs, our aim was to determine the usefulness of a new Web-based telemonitoring system, connecting patients provided with self-measurement devices and care managers via mobile phone text messages, as a tool for SP. METHODS: A single-blind, randomized controlled, clinical trial of 203 acute coronary syndrome (ACS) survivors, was conducted at a hospital in Madrid, Spain. All patients received lifestyle counseling and usual-care treatment. Patients in the telemonitoring group (TMG) sent, through mobile phones, weight, heart rate, and blood pressure (BP) weekly, and capillary plasma lipid profile and glucose monthly. A cardiologist accessed these data through a Web interface and sent recommendations via short message service. Main outcome measures were BP, body mass index (BMI), smoking status, low-density lipoprotein-cholesterol (LDL-c), and glycated hemoglobin A1c (HbA1c). RESULTS: At 12-month followup, TMG patients were more likely (RR = 1.4; 95% CI = 1.1-1.7) to experience improvement in cardiovascular risk factors profile than control patients (69.6% vs 50.5%, P = .010). More TMG patients achieved treatment goals for BP (62.1% vs 42.9%, P = .012) and HbA1c (86.4% vs 54.2%, P = .018), with no differences in smoking cessation or LDL-c. Body mass index was significantly lower in TMG (-0.77 kg/m² vs +0.29 kg/m², P = .005). CONCLUSIONS: A telemonitoring program, via mobile phone messages, appears to be useful for improving the risk profile in ACS survivors and can be an effective tool for secondary prevention, especially for overweight patients.

[Primary percutaneous angioplasty. An analysis of reperfusion delays, their determining factors and their prognostic implications]. / Angioplastia primaria en nuestro medio. Análisis de los retrasos hasta la reperfusión, sus condicionantes y su implicación pronóstica.

INTRODUCTION AND OBJECTIVES: The optimum treatment for patients with ST-segment elevation acute myocardial infraction (AMI) is primary percutaneous coronary intervention (PCI), provided that the door-to-balloon time is less than 90 min. The aims of this study were to determine actual treatment times in our patients, to investigate the effect of different factors in reducing those times, and to evaluate the impact of any delay on prognosis. METHODS: The study involved patients who underwent primary or rescue PCI at our center between January 2005 and October 2007. Treatment times, clinical and angiographic characteristics, and follow-up findings at 1 and 12 months were recorded prospectively. RESULTS: Overall, 389 PCIs were performed: 361 primary and 28 rescue interventions. The median total duration of ischemia was 235 [interquartile range, 170-335] min. The median door-to-balloon time was 79 [53-104] min. The door-to-balloon time was shorter when the ambulance service was able to notify the on-duty cardiologist, who alerted the interventional cardiology team. The difference was 30 [60-90] min (P< .01). Patients who arrived at the emergency department by their own means had the longest door-to-balloon time (100 min vs. 74 min; P< .01). A door-to-balloon time >120 min was associated with higher mortality at 30 days; multivariate analysis showed a clearly increasing trend. CONCLUSIONS: The door-to-balloon time at our center was in line with current recommendations, with the time being markedly shorter for patients for whom the ambulance service was able to give advanced warning. A shorter time was associated with a trend towards lower 30-day mortality.