Repeated occurrence of severe hypotension associated with azithromycin infusion in a patient with fulminant myocarditis: a case report.

Background: Intravenous administration of azithromycin has been linked to severe hypotension in some case reports in the past. We report a further case of profound shock requiring excessive use of vasopressors and extracorporeal membrane oxygenation (ECMO). Case summary: An 18-year-old Caucasian male was admitted due to fulminant myocarditis and signs of cardiogenic shock. He had to be put on venoarterial ECMO only hours after admission. Due to the occurrence of disseminated intravascular coagulation and heparin-induced thrombocytopenia, haemodynamic support was discontinued on Day 8. On Day 11 of his stay, the patient started to exhibit signs of severe infection and a single 1500 mg dose of azithromycin was prescribed. Immediately after starting the infusion, the patient developed profound hypotension and signs of cardiogenic shock. Consecutively, venoarterial ECMO had to be re-established, and the azithromycin infusion was stopped in the process. It took the restart of the compound to recognize the connection between the administration of the therapy and the occurrence of cardiogenic shock. After discontinuing azithromycin, no further sudden hypotensive episodes were recorded, and the patient received left ventricular assist device implantation as a bridge to recovery or transplant. Discussion: Rapid-onset hypotension appears to be a very rare but important adverse drug reaction associated with intravenous administration of azithromycin. Factors such as preceding infection and reduced biventricular function may facilitate the described occurrence.

Mechanical Circulatory Support Systems in Fulminant Myocarditis: Recent Advances and Outlook.

Background: Fulminant myocarditis (FM) constitutes a severe and life-threatening form of acute cardiac injury associated with cardiogenic shock. The condition is characterised by rapidly progressing myocardial inflammation, leading to significant impairment of cardiac function. Due to the acute and severe nature of the disease, affected patients require urgent medical attention to mitigate adverse outcomes. Besides symptom-oriented treatment in specialised intensive care units (ICUs), the necessity for temporary mechanical cardiac support (MCS) may arise. Numerous patients depend on these treatment methods as a bridge to recovery or heart transplantation, while, in certain situations, permanent MCS systems can also be utilised as a long-term treatment option. Methods: This review consolidates the existing evidence concerning the currently available MCS options. Notably, data on venoarterial extracorporeal membrane oxygenation (VA-ECMO), microaxial flow pump, and ventricular assist device (VAD) implantation are highlighted within the landscape of FM. Results: Indications for the use of MCS, strategies for ventricular unloading, and suggested weaning approaches are assessed and systematically reviewed. Conclusions: Besides general recommendations, emphasis is put on the differences in underlying pathomechanisms in FM. Focusing on specific aetiologies, such as lymphocytic-, giant cell-, eosinophilic-, and COVID-19-associated myocarditis, this review delineates the indications and efficacy of MCS strategies in this context.

Lactate as a Predictor of 30-Day Mortality in Cardiogenic Shock.

Background/Objectives: This study sought to evaluate the efficacy of various lactate measurements within the first 24 h post-intensive care unit (ICU) admission for predicting 30-day mortality in cardiogenic shock patients. It compared initial lactate levels, 24 h levels, peak levels, and 24 h clearance, alongside the Simplified Acute Physiology Score 3 (SAPS3) score, to enhance early treatment decision-making. Methods: A retrospective analysis of 64 patients assessed the prognostic performance of lactate levels and SAPS3 scores using logistic regression and AUROC calculations. Results: Of the baseline parameters, only the SAPS3 score predicted survival independently. The lactate level after 24 h (LL) was the most accurate predictor of mortality, outperforming initial levels, peak levels, and 24 h-clearance, and showing a significant AUROC. LL greater than 3.1 mmol/L accurately predicted mortality with high specificity and moderate sensitivity. Conclusions: Among lactate measurements for predicting 30-day mortality in cardiogenic shock, the 24 h lactate level was the most effective one, suggesting its superiority for early prognostication over initial or peak levels and lactate clearance.

Long-term outcome of bicuspid aortic valve disease.

AIMS: Bicuspid aortic valve (BAV) is a common congenital condition that is frequently associated with aortic stenosis (AS) and aortic regurgitation (AR), as well as aortic aneurysms, but specific outcome data are scarce. The present study sought to assess outcomes in a large cohort of consecutive patients with BAV. METHODS AND RESULTS: A total of 581 consecutive patients (median age 29 years, 157 female) with BAV were included in the study and followed prospectively in a heart valve clinic follow-up programme. The overall survival rate after 10 years was 94.5%. During follow-up, 158 patients developed an indication for surgery. Event-free survival rates were 97%, 94%, 87%, and 73% at 1, 2, 5, and 10 years, respectively. In the multivariable analysis, event rates were independently predicted by AS [subdistribution hazard ratio (SHR) 2.3 per degree of severity], AR (SHR 1.5 per degree of severity), baseline aortic dilatation ≥ 40 mm (SHR 1.9), and age (SHR 1.3) (P < 0.001). CONCLUSION: BAV disease is associated with a high rate of cardiac events, but state-of-the-art care results in good survival with low rates of infective endocarditis, aortic dissection, and sudden death. Incremental degrees of AS and regurgitation, the presence of aortic dilatation, and age are predictive of cardiac events.

Left atrial size predicts outcome in severe but asymptomatic mitral regurgitation.

Patients with severe asymptomatic primary mitral regurgitation (MR) can be safely managed with an active surveillance strategy. Left atrial (LA) size is affected by MR severity, left ventricular function and is also associated with the risk of atrial fibrillation and may be an integrative parameter for risk stratification. The present study sought to determine the predictive value of LA size in a large series of asymptomatic patients with severe MR. 280 consecutive patients (88 female, median age 58 years) with severe primary MR and no guideline-based indications for surgery were included in a follow-up program until criteria for mitral surgery were reached. Event-free survival was determined and potential predictors of outcome were assessed. Survival free of any indication for surgery was 78% at 2 years, 52% at 6 years, 35% at 10 years and 19% at 15 years, respectively. Left atrial (LA) diameter was the strongest independent echocardiographic predictor of event-free survival with incremental predictive value for the thresholds of 50, 60 and 70 mm, respectively. In a multivariable analysis that encompassed age at baseline, previous history of atrial fibrillation, left ventricular end systolic diameter), LA diameter, sPAP > 50 mmHg and year of inclusion, LA diameter was the strongest independent echocardiographic predictor of event-free survival (adjusted HR = 1.039, p < 0.001). LA size is a simple and reproducible predictor of outcome in asymptomatic severe primary MR. In particular, it may help to identify patients who may benefit from early elective valve surgery in heart valve centers of excellence.

Open Transcatheter Mitral Valve Implantation Into the Native Mitral Valve for Inoperable "Big MAC".

Because of the growing population of older adult patients, the prevalence of severe mitral annulus calcification ("big MAC") is increasing. The surgical techniques used to treat big MACs are technically demanding; despite the technical aspect, up to one-third of patients are considered too high risk for conventional surgery but are candidates for the coulisse technique, which is a procedure that implants a transcatheter valve into a native mitral annulus. The anterior leaflet is unfolded, thus reducing the risk of obstructing the left ventricular outflow tract and for paravalvular leak and avoiding valve migration. Preoperative planning, based on a computed tomography scan, is mandatory.

Isolated tricuspid valve regurgitation: old concepts, new insights and innovation.

: Tricuspid valve regurgitation is usually progressive and associated with reduced long-term survival. International guidelines recommend surgery in cases of isolated severe regurgitation associated with symptoms or progressive worsening of right ventricular function. In addition, several percutaneous strategies have been reported with promising results in the last decade. The aim of the present review is to summarize the current state of the art in the management of isolated functional or degenerative tricuspid valve insufficiency, from the preoperative assessment to the results of both surgical and transcatheter approaches and explore future directions.

[Cardiogenic shock]. / Kardiogener Schock.

Cardiogenic shock (CS) is defined as end-organ hypoperfusion as the consequence of primary myocardial dysfunction. Among the diagnostic criteria are a systolic blood pressure < 90 mmHg, acute renal failure (oligoanuria), ischemic hepatitis, cyanosis and cold, clammy skin. Accepted hemodynamic cutoffs are a cardiac index < 2,2 (l/min)/m2 and a pulmonary capillary wedge pressure > 15 mmHg. It should be acknowledged, that a normal blood pressure does not rule out CS; there is a nonhypotensive variant of CS demonstrating all the signs mentioned above (including elevated lactate levels) while the blood pressure is compensated due to vasoconstriction.The single most frequent cause of CS is pump failure in the setting of an acute myocardial infarction and its mortality rate has been lowered to 40-50%, owing to the widespread availability of primary PCI. Regarding PCI, it has been demonstrated recently that a "culprit-lesion only strategy" should be followed in the setting of CS. Other important causes of CS to take into account are mechanical complications of myocardial infarction (papillary and ventricular septal rupture as well as rupture of the myocardial free wall leading to tamponade), valvular heart disease (mostly decompensated aortic stenosis) as well as myocarditis and end stage cardiomyopathy.The diagnosis of CS is made by patient history, physical examination, ECG, echocardiography and coronary angiography. Echocardiography should always be performed before coronary angiography because, in the case of mechanical complications, it significantly alters the management of the patients. Patients with clinical signs of CS but paradoxically preserved ejection fraction must be thoroughly evaluated for the presence of a papillary muscle rupture, particularly in the setting of a lateral wall infarction.Noradrenaline and dobutamine are the first-line agents for medical stabilization. When such conventional measures fail, extracorporeal support devices such as ECMO or Impella© may be used. Currently, trials are underway to assess wheter these devices confer a survival benefit in this high-risk population.

Clinical outcomes after TAVR with heparin or bivalirudin as periprocedural anticoagulation in patients with and without peripheral arterial disease: Results from the BRAVO-3 randomized trial.

OBJECTIVES: This study sought to investigate the clinical outcomes of patients with and without peripheral artery disease (PAD) in the BRAVO-3 trial with respect to the effect of bivalirudin versus unfractionated heparin (UFH). BACKGROUND: PAD is found frequently in patients undergoing transcatheter aortic valve replacement (TAVR) and is reported to confer an increased risk of adverse events. It is unknown whether patients with and without PAD may demonstrate a differential response to bivalirudin versus UFH. METHODS: BRAVO-3 was a randomized multicenter trial comparing transfemoral TAVR with bivalirudin versus UFH (31 centers, n = 802). Major adverse cardiovascular events (MACE) were a composite of 30-day death, myocardial infarction, or cerebrovascular accidents (CVA). Net adverse cardiovascular events (NACE) were a composite of major bleeding or MACE. RESULTS: The total cohort included 119 patients with PAD. Vascular complications occurred significantly more frequently in patients with PAD both in-hospital (25.2 vs. 16.7%; OR 1.68) and at 30 days (29.4 vs. 17.3%; OR 1.99). No significant differences were observed regarding mortality, NACE, MACE, major bleeding or CVA with bivalirudin versus UFH among patients with or without PAD. In patients with PAD, bivalirudin was associated with an increased risk of minor vascular complications at 30 days. CONCLUSIONS: Patients with PAD undergoing transfemoral TAVR did not exhibit an increased risk of any major adverse events, according to the procedural anticoagulant randomization. However, patients treated with Bivalirudin had significantly higher rates of minor vascular complications.

Off-pump tricuspid valve repair by automated sutured tricuspid annular plication via transatrial cannulation: preclinical ex vivo and in vivo results.

OBJECTIVES: Surgical repair is considered the gold standard treatment for severe symptomatic tricuspid valve (TV) regurgitation. However, patients undergoing isolated surgical tricuspid repair face a high perioperative mortality while long-term data on interventional treatment options are currently missing. We investigated a novel, minimally invasive approach for transatrial off-pump beating-heart tricuspid annular plication based on the surgical Hetzer repair. METHODS: TV annular plication for the creation of a double-orifice valve using novel devices for automated annular suturing was performed in 10 human heart specimens in an ex vivo perfusion model under endoscopic guidance. Additionally, the technique was tested in an in vivo porcine model using the transatrial access under echocardiographic and fluoroscopic guidance. RESULTS: Endoscopically guided conduction of the procedure was successful in all 10 human heart specimens in the ex vivo perfusion model with 1 observed suture pull-through of 60 sutures placed (1.7%). TV measurements yielded significant reductions of the TV septal-lateral diameter (50.9 ± 7.3 vs 42.6 ± 7.9 mm; P = 0.015) and the TV area (1208 ± 399 vs 193 ± 122 mm2; P < 0.0001). TV plication without direct vision using device-embedded intracardiac echocardiography, epicardial echocardiography and fluoroscopy was feasible in both acute animals with no observed device-related adverse events. CONCLUSIONS: Successful plication was completed in 10 ex vivo human hearts, additionally proof-of-concept was conducted in 2 animals. We herein present encouraging early preclinical results of a novel minimally invasive technique for TV repair, which warrants further investigation.

Prognostic Value of Right Ventricular Dysfunction and Tricuspid Regurgitation in Patients with Severe Low-Flow Low-Gradient Aortic Stenosis.

Long and mid-term data in Low-Flow Low-Gradient Aortic Stenosis (LFLG-AS) are scarce. The present study sought to identify predictors of outcome in a sizeable cohort of patients with LFLG-AS. 76 consecutive patients with LFLG-AS (defined by a mean gradient <40 mmHg, an aortic valve area ≤1 cm2 and an ejection fraction ≤50%) were prospectively enrolled and followed at regular intervals. Events defined as aortic valve replacement (AVR) and death were assessed and overall survival was determined. 44 patients underwent AVR (10 transcatheter and 34 surgical) whilst intervention was not performed in 32 patients, including 9 patients that died during a median waiting time of 4 months. Survival was significantly better after AVR with survival rates of 91.8% (CI 71.1-97.9%), 83.0% (CI 60.7-93.3%) and 56.3% (CI 32.1-74.8%) at 1,2 and 5 years as compared to 84.3% (CI 66.2-93.1%), 52.9% (CI 33.7-69.0%) and 30.3% (CI 14.6-47.5%), respectively, for patients managed conservatively (p = 0.017). The presence of right ventricular dysfunction (HR 3.47 [1.70-7.09]) and significant tricuspid regurgitation (TR) (HR 2.23 [1.13-4.39]) independently predicted overall mortality while the presence of significant TR (HR 3.40[1.38-8.35]) and higher aortic jet velocity (HR 0.91[0.82-1.00]) were independent predictors of mortality and survival after AVR. AVR is associated with improved long-term survival in patients with LFLG-AS. Treatment delays are associated with excessive mortality, warranting urgent treatment in eligible patients. Right ventricular involvement characterized by the presence of TR and/or right ventricular dysfunction, identifies patients at high risk of mortality under both conservative management and after AVR.

Concomitant Transapical Transcatheter Aortic Valve Implantation and Transapical Mitral Valve Repair With NeoChord Implantation.

One-third of the patients with severe symptomatic aortic valve stenosis (sAS) present with hemodynamic relevant mitral valve insufficiency (rMI). In patients who undergo conventional surgery, the rMI never would be left untreated; however, in cases of transcatheter aortic valve implantation (TAVI), the impact of rMI is often overlooked and left untreated. The combination of transapical TAVI (TA-TAVI) and NeoChord implantation represents a novel, promising therapeutic option for high-risk-surgery patients with sAS and rMI due to a prolapsed or flailed leaflet. This case report describes 2 patients (1 male, 1 female; mean age 82 years) who underwent TA-TAVI and concomitant NeoChord implantation at our institute. Both presented with sAS and rMI due to a prolapse of the P2 segment of the mitral valve. At first, the TA-TAVI was implanted under angio-guidance, followed by three-dimensional echo-guided implantation of the NeoChords, through the same approach, which was slightly posterior and lateral to the apex. TA-TAVI using an Edwards Sapien 3 (26 mm, n = 1 and 29 mm, n = 1) and NeoChord implantation (2 in the first and 3 in the second patient) was successful in both cases. Post-intervention discharge echo indicated no paravalvular or central insufficiency after the procedure and only a trace of mitral valve insufficiency. TA-TAVI and concomitant NeoChord implantation is a feasible and promising treatment option for high-risk patients with rMI. Despite its technical demands, in experienced hands, it is a safe procedure for those not well suited for surgical intervention.

Outcomes of Patients With Asymptomatic Aortic Stenosis Followed Up in Heart Valve Clinics.

Importance: The natural history and the management of patients with asymptomatic aortic stenosis (AS) have not been fully examined in the current era. Objective: To determine the clinical outcomes of patients with asymptomatic AS using data from the Heart Valve Clinic International Database. Design, Setting, and Participants: This registry was assembled by merging data from prospectively gathered institutional databases from 10 heart valve clinics in Europe, Canada, and the United States. Asymptomatic patients with an aortic valve area of 1.5 cm2 or less and preserved left ventricular ejection fraction (LVEF) greater than 50% at entry were considered for the present analysis. Data were collected from January 2001 to December 2014, and data were analyzed from January 2017 to July 2018. Main Outcomes and Measures: Natural history, need for aortic valve replacement (AVR), and survival of asymptomatic patients with moderate or severe AS at entry followed up in a heart valve clinic. Indications for AVR were based on current guideline recommendations. Results: Of the 1375 patients included in this analysis, 834 (60.7%) were male, and the mean (SD) age was 71 (13) years. A total of 861 patients (62.6%) had severe AS (aortic valve area less than 1.0 cm2). The mean (SD) overall survival during medical management (mean [SD] follow up, 27 [24] months) was 93% (1%), 86% (2%), and 75% (4%) at 2, 4, and 8 years, respectively. A total of 104 patients (7.6%) died under observation, including 57 patients (54.8%) from cardiovascular causes. The crude rate of sudden death was 0.65% over the duration of the study. A total of 542 patients (39.4%) underwent AVR, including 388 patients (71.6%) with severe AS at study entry and 154 (28.4%) with moderate AS at entry who progressed to severe AS. Those with severe AS at entry who underwent AVR did so at a mean (SD) of 14.4 (16.6) months and a median of 8.7 months. The mean (SD) 2-year and 4-year AVR-free survival rates for asymptomatic patients with severe AS at baseline were 54% (2%) and 32% (3%), respectively. In those undergoing AVR, the 30-day postprocedural mortality was 0.9%. In patients with severe AS at entry, peak aortic jet velocity (greater than 5 m/s) and LVEF (less than 60%) were associated with all-cause and cardiovascular mortality without AVR; these factors were also associated with postprocedural mortality in those patients with severe AS at baseline who underwent AVR (surgical AVR in 310 patients; transcatheter AVR in 78 patients). Conclusions and Relevance: In patients with asymptomatic AS followed up in heart valve centers, the risk of sudden death is low, and rates of overall survival are similar to those reported from previous series. Patients with severe AS at baseline and peak aortic jet velocity of 5.0 m/s or greater or LVEF less than 60% have increased risks of all-cause and cardiovascular mortality even after AVR. The potential benefit of early intervention should be considered in these high-risk patients.

Long-Term Outcome of Active Surveillance in Severe But Asymptomatic Primary Mitral Regurgitation.

OBJECTIVES: This study sought to assess the long-term outcome of active surveillance in these patients. BACKGROUND: The optimal timing of mitral valve surgery in asymptomatic primary mitral regurgitation (MR) remains controversial. METHODS: Between 1997 and 2015, 280 consecutive patients with severe asymptomatic primary MR were enrolled in our heart valve clinic follow-up program. They were prospectively followed up every 6 months clinical and echocardiographical examinations until surgical criteria were reached. Event-free survival and overall survival as compared with the age- and gender-matched general population were assessed. RESULTS: During a median potential follow-up of 93.4 (quartiles 55.3 to 152.9) months, 161 patients developed an indication for surgery and 13 patients died. Event-free survival rates were 78.0% (95% confidence interval [CI]: 73.2% to 83.2%) at 2 years, 52.2% (95% CI: 46.3% to 59.0%) at 6 years, 35.5% (95% CI: 29.3% to 43.1%) at 10 years, and 18.7% (95% CI: 12.3% to 28.5%) at 15 years. Overall survival rate was 99.6% (95% CI: 98.9% to 100%) at 2 years, 94.6% (95% CI: 91.7% to 97.6%) at 6 years, 85.6% (95% CI: 80.3% to 91.2%) at 10 years, and 74.5% (95% CI: 66.6% to 83.4%) at 15 years. Overall survival of patients managed according to an active surveillance strategy was comparable with the expected cumulative survival and early survival rates were even better in the study population (standardized mortality ratio: 0.667; 95% CI: 0.463 to 0.963; p = 0.013). CONCLUSIONS: Patients with severe asymptomatic primary MR may remain free of indications for surgery for extensive periods of time. In such patients, active surveillance performed in experienced centers is associated with a favorable prognosis, resulting in timely referral to surgery, excellent long-term survival, and good surgical outcomes.

Prognostic relevance of mitral and tricuspid regurgitation in patients with severe aortic stenosis.

Aims: Although concomitant mitral regurgitation (MR) and tricuspid regurgitation (TR) are frequently present in patients with aortic stenosis (AS), outcome data are scarce and treatment strategies are controversial. The aim of the present study was to assess the presentation and outcome of patients with AS and coexisting MR and TR. Methods and results: Eighty-nine consecutive patients with severe AS and at least moderate MR (72 functional and 17 degenerative) were included and followed. Seventy-five patients were symptomatic at presentation. Sixty of these had severe symptoms (New York Heart Association class ≥3). Nine additional patients had an indication for valve procedures during follow-up. However, 35 patients were managed conservatively. Isolated aortic valve intervention was performed in 29 patients (22 valve replacement and 7 transcatheter aortic valve replacement) and concomitant mitral valve surgery in 20 patients. For the assessment of outcome, overall survival (i.e. time from study entry to death from any cause) was assessed: adjusted survival was significantly higher for patients undergoing any valve procedure as compared with patients managed conservatively (P = 0.032). Surgical treatment of severe concomitant MR was associated with improved survival in an unadjusted population but did not reach statistical significance after propensity adjustment. 14 of 36 patients who had concomittant moderate-to-severe tricuspid regurgitation (TR) underwent surgery of which 7 (50 %) died within 3 months postoperatively. On the other hand, only 1 of 35 (3%) with no or mild TR undergoing surgery died within 3 months post-operatively (P < 0.001). Conclusion: Presence of MR in patients with severe AS characterizes a high-risk population. Timely aortic valve intervention confers a survival benefit and concomitant mitral valve surgery should be considered according to operative risk. The additional presence of significant TR is associated with dismal outcomes, regardless of the treatment strategy.

Asymptomatic Severe Aortic Stenosis in the Elderly.

OBJECTIVES: This study sought to assess the natural history and optimal timing of surgery in elderly patients with severe asymptomatic aortic stenosis (AS). BACKGROUND: AS is increasingly diagnosed in an aging population, and large numbers of elderly patients are undergoing aortic valve procedures. However, the average age of patients represented in most natural history studies on AS is between 60 and 70 years. METHODS: A total of 103 consecutive patients >70 years of age (51 female; mean age 77 ± 5 years) with asymptomatic severe AS (peak aortic jet velocity [AV-Vel] 4.7 ± 0.6 m/s) were prospectively followed. RESULTS: During follow-up, 91 events occurred, including an indication for aortic valve replacement in 82 patients and cardiac deaths in 9, respectively. Event-free survival was 73%, 43%, 23%, and 16% at 1, 2, 3, and 4 years, respectively. Physical mobility was impaired in 29% of the patients, and symptom onset was severe (New York Heart Association functional class ≥III) in 43% of those who developed symptoms. Patients with AV-Vel ≥5.0 m/s had event-free survival rates of 21% and 6% at 2 and 4 years, respectively, compared with 57% and 23% for patients with AV-Vel <5.0 m/s (p < 0.001). Seventy-one patients underwent aortic valve replacement, and post-operative survival was 89% and 77% after 1 and 3 years, respectively. CONCLUSIONS: In elderly patients with severe but asymptomatic AS, mild symptoms may be difficult to detect, particularly when mobility is impaired and severe symptom onset is common, warranting close clinical follow-up. Furthermore, a very high event rate can be expected, and cardiac deaths are not infrequent. Thus, elective aortic valve procedures may be considered in selected elderly patients at low procedural risk.

Role of a heart valve clinic programme in the management of patients with aortic stenosis.

AIMS: We sought to assess the efficacy of a heart valve clinic (HVC) follow-up programme for patients with severe aortic stenosis (AS). METHODS AND RESULTS: Three hundred and eighty-eight consecutive patients with AS (age 71 ± 10 years; aortic-jet velocity 5.1 ± 0.6 m/s) and an indication for aortic valve replacement (AVR) were included. Of these, 290 patients presented with an indication for surgery at their first visit at the HVC and 98 asymptomatic patients who had been enrolled in an HVC monitoring programme developed indications for surgery during follow-up. Time to symptom detection was significantly longer in patients that presented with symptoms at baseline (352 ± 471 days) than in patients followed in the HVC (76 ± 75 days, P < 0.001). Despite being educated to recognize and promptly report new symptoms, 77 of the 98 patients in the HVC programme waited until the next scheduled consultation to report them. Severe symptom onset (NYHA or CCS Class ≥III) was present in 61% of patients being symptomatic at the initial visit and in 34% of patients in the HVC programme (P < 0.001). CONCLUSION: Delays in referral and symptom reporting as well as symptom denial are common in patients with AS. These findings support the concept of risk stratification to identify patients who may benefit from elective surgery. A structured HVC programme results in the detection of symptoms at an earlier and less severe stage and thus in an optimized timing of surgery.

Outcome of combined stenotic and regurgitant aortic valve disease.

OBJECTIVES: This study sought to describe the natural history of combined stenotic and regurgitant aortic valve disease. BACKGROUND: Data on outcome and prognostic factors in combined aortic valve disease are scarce. METHODS: This study prospectively followed 71 consecutive asymptomatic patients (21 women, age 52 ± 17 years) with at least moderate aortic stenosis in combination with at least moderate aortic regurgitation and preserved left ventricular function (ejection fraction ≥55%). RESULTS: During a median potential follow-up of 8.9 years, 50 patients developed an indication for aortic valve replacement and no cardiac deaths were observed. Overall event rates were high with an event-free survival for the entire patient population of 82 ± 5%, 62 ± 6%, 49 ± 6%, 33 ± 6%, and 19 ± 5% at 1, 2, 3, 4, and 6 years, respectively. There was 1 operative and no post-operative deaths. Peak aortic jet velocity (AV-Vel) independently predicted event-free survival. Patients with an AV-Vel between 3 and 3.9 m/s had an event-free survival of 94 ± 4%, 88 ± 6%, 65 ± 9%, and 51 ± 9% after 1, 2, 4, and 6 years, respectively, compared with 92 ± 4%, 67 ± 7%, 38 ± 8%, and 12 ± 6% for patients with an AV-Vel between 4 and 4.9 m/s and 67 ± 8%, 39 ± 10%, 17 ± 9%, and 0% for patients with an AV-Vel ≥5 m/s (p < 0.0001). CONCLUSIONS: Asymptomatic patients with combined aortic valve disease can be safely followed until surgical criteria defined for aortic stenosis, aortic regurgitation, or the aorta are reached. However, high event rates can be expected even in younger patients and those with only moderate disease. AV-Vel, which reflects both stenosis and regurgitant severity, provides an objective and easily assessable predictive parameter.

Natural history of very severe aortic stenosis.

BACKGROUND: We sought to assess the outcome of asymptomatic patients with very severe aortic stenosis. METHODS AND RESULTS: We prospectively followed 116 consecutive asymptomatic patients (57 women; age, 67 + or - 16 years) with very severe isolated aortic stenosis defined by a peak aortic jet velocity (AV-Vel) > or = 5.0 m/s (average AV-Vel, 5.37 + or - 0.35 m/s; valve area, 0.63 + or - 0.12 cm(2)). During a median follow-up of 41 months (interquartile range, 26 to 63 months), 96 events occurred (indication for aortic valve replacement, 90; cardiac deaths, 6). Event-free survival was 64%, 36%, 25%, 12%, and 3% at 1, 2, 3, 4, and 6 years, respectively. AV-Vel but not aortic valve area was shown to independently affect event-free survival. Patients with an AV-Vel > or = 5.5 m/s had an event-free survival of 44%, 25%, 11%, and 4% at 1, 2, 3, and 4 years, respectively, compared with 76%, 43%, 33%, and 17% for patients with an AV-Vel between 5.0 and 5.5 m/s (P<0.0001). Six cardiac deaths occurred in previously asymptomatic patients (sudden death, 1; congestive heart failure, 4; myocardial infarction, 1). Patients with an initial AV-Vel > or = 5.5 m/s had a higher likelihood (52%) of severe symptom onset (New York Heart Association or Canadian Cardiovascular Society class >II) than those with an AV-Vel between 5.0 and 5.5 m/s (27%; P=0.03). CONCLUSIONS: Despite being asymptomatic, patients with very severe aortic stenosis have a poor prognosis with a high event rate and a risk of rapid functional deterioration. Early elective valve replacement surgery should therefore be considered in these patients.