New insights into the hemodynamics of pulmonary homograft patients under stress echocardiography: The contribution of pressure recovery.

BACKGROUND: The importance of pulmonary artery pressure recovery (PR) in patients with Ross procedures in whom a homograft substitutes the resected pulmonary valve, is unknown. The aim of the study was to evaluate the occurrence and extent of PR in the pulmonary artery in 65 asymptomatic patients with pulmonary homograft after Ross surgery during rest and exercise. METHODS: Stress echocardiography was performed in 65 pulmonary homograft patients and 31 controls with native pulmonary valves up to 75 W. Right ventricular systolic pressure (RVSP), transvalvular flow, mean pressure gradient (Pmean ), valve resistance, and RV stroke work were determined in the exercise (max. 75 W) and recovery phases in increments of 25 W each. RESULTS: Pulmonary homografts demonstrated significantly elevated Pmean compared to controls at all stages. When considering pressure recovery (absolute and relative PR at rest 3.8 ± 1.8 mm Hg, 42.6 ± 7.2%, respectively) and transvalvular energy loss (EL; at rest 4.5 ± 4.3 mm Hg) the homograft hemodynamics reached the level of controls. In a subgroup of patients with tricuspid regurgitation, resting RVSP was the same in homograft patients and controls (21.3 ± 6.1 vs. 20.4 ± 6.3, p = .62), despite significant different Pmax values. CONCLUSIONS: Ross patients with pulmonary homograft showed systematically increased hemodynamic parameters compared to normal pulmonary valves. These differences were abolished when PR was considered for homograft patients. The equality of RVSP values at rest in both groups shows non-invasive evidence for PR in the pulmonary system after homograft implantation. Therefore, PR appears to be an important measure in calculating the actual hemodynamics in pulmonary homografts.

Systemic thrombo-embolic events in a middle-aged male with Loeffler endocarditis without peripheral eosinophilia-a case report.

BACKGROUND: Loeffler-endocarditis (LE) is considered a chronic restrictive cardiomyopathy and manifestation of eosinophilic myocarditis characterized by eosinophilic infiltration. LE is a rare underdiagnosed disease and associated with high morbidity and mortality. CASE PRESENTATION: We report a case of a 46-year-old man suffering from LE associated with thromboembolic events without peripheral eosinophilia. The patient presented with typical clinical signs of acute onset of limb ischaemia, predominantly on the right limb, indicating immediate iliacal thrombectomy and due to a severe compartment syndrome additional fasciotomy. Total occlusion also of left popliteal artery suggesting an impaired chronic and aggravated impaired perfusion indicated also urgent left sided revascularization. Subsequent echocardiography revealed severe left ventricular dysfunction with a striking amount of spontaneous echo-contrast, noticeable in the left ventricular cavity. Furthermore the initial CT scan demonstrated asymptomatic left kidney- and brain infarctions. Diagnostic workup including endomyocardial biopsy (EMB) of the left ventricle, uncovered an underlying LE without peripheral eosinophilia. CONCLUSIONS: This case demonstrates and highlights the findings, treatment and outcome of a patient with LE and associated thrombo-embolic events without peripheral eosinophilia and emphazises the importance of awareness for LE in patients presenting with an acute cardiac decompensation and thrombo-embolic events. EMB should be performed early in unstable patients unsuitable for cardiovascular magnetic resonance imaging.

Prognostic impact of impaired left ventricular midwall function during progression of aortic stenosis.

OBJECTIVE: In hypertension, indexes of midwall left ventricular (LV) function may identify patients at higher cardiovascular (CV) risk independent of normal LV ejection fraction (EF). We analyzed the association of baseline and new-onset LV midwall dysfunction with CV outcome in a large population of patients with asymptomatic aortic stenosis (AS). METHODS: One thousand four hundred seventy-eight patients with asymptomatic AS and normal EF (≥50%) at baseline in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a median of 4.3 years. LV systolic function was assessed by biplane EF and midwall shortening (MWS, low if <14% in men/16% in women) at baseline and annual echocardiographic examinations. RESULTS: One hundred twenty-three CV deaths and heart failure hospitalizations occurred during follow-up. In Cox analyses, adjusting for age, gender, body mass index, hypertension, EF, AS severity, LV hypertrophy and systemic arterial compliance, low baseline MWS predicted 61% higher risk of a major CV event and a twofold higher risk of death and heart failure hospitalization (P < .05). New-onset low MWS developed in 574 patients, particularly in elderly women with higher blood pressure and more severe AS (P < .05). In time-varying Cox analysis, new-onset low MWS was associated with a twofold higher risk of CV death and heart failure hospitalization, independent of changes over time in EF, AS severity, LV hypertrophy and systemic arterial compliance (P < .05). CONCLUSIONS: Low MWS develops in a large proportion of patients with AS and normal EF during valve disease progression and is a marker of increased CV risk.

Short-term use of "ECMELLA" in the context of fulminant eosinophilic myocarditis with cardiogenic shock.

BACKGROUND: Eosinophilic myocarditis (EM) is a rare form of myocarditis. Clinical presentation is various, includes cardiogenic shock and can often be fatal. Diagnosis is based on myocardial eosinophilic infiltration in endomyocardial biopsy. Mechanical circulatory support (MCS) is often required in patients suffering from severe cardiogenic shock. Among the available MCS options the "ECMELLA" concept, a combination of left ventricular venting by Impella® device and extracorporeal life support (ECLS) is possibly able to provide the necessary time frame for diagnostics and initiation of anti-inflammatory medication in patients with fulminant myocarditis. CASE PRESENTATION: We report a case of a 38-year-old woman who was presented to us in severe cardiogenic shock, quickly requiring hemodynamic support by an Impella CP® device. Further dramatic hemodynamic deterioration accompanied by multi-organ dysfunction required escalation of MCS via ECLS as veno-arterial extracorporeal membrane oxygenation (VA-ECMO). After histopathological diagnosis of EM, our patient was put on immunosuppressive therapy with prednisolone. Recovery of both right and left ventricular function allowed explanation of VA-ECMO on day 4 and further hemodynamic improvement allowed removal of the Impella® device on day 9. The patient was discharged after 7 weeks with fully restored cardiac function and in a good neurological state. CONCLUSIONS: In severe cardiac shock due to fulminant EM the ECMELLA concept as bridge-to-recovery seems to be a valid option to provide the required time for diagnostics and specific therapy.

Prognostic value of energy loss index in asymptomatic aortic stenosis.

BACKGROUND: Aortic valve area index adjusted for pressure recovery (energy loss index [ELI]) has been suggested as a more accurate measure of aortic stenosis (AS) severity, but its prognostic value has not been determined in a prospective study. METHODS AND RESULTS: The relation between baseline ELI and rate of aortic valve events and combined total mortality and hospitalization for heart failure resulting from the progression of AS was assessed by multivariate Cox regression and reclassification analysis in 1563 patients with initial asymptomatic AS in the Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study. During 4.3 years follow-up, a total of 498 aortic valve events and 181 combined total mortalities and hospitalizations for heart failure caused by the progression of AS occurred. In Cox regression analyses, 1-cm(2)/m(2) lower baseline ELI predicted a 2-fold higher risk both for aortic valve events and for combined total mortality and hospitalization for heart failure independently of baseline peak aortic jet velocity or mean aortic gradient and independently of aortic root size (all P<0.05). In reclassification analysis, ELI improved the prediction of aortic valve events by 13% (95% confidence interval, 5-19), whereas the prediction of combined total mortality and hospitalization for heart failure resulting from the progression of AS did not improve significantly. CONCLUSIONS: In asymptomatic AS patients without known atherosclerotic disease or diabetes mellitus, ELI provides independent and additional prognostic information to that derived from conventional measures of AS severity, suggesting that ELI should be measured in such patients. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00092677.

Acute Lymphocytic Myocarditis in a Young Male Post-COVID-19.

Background: Lymphocytic myocarditis is a rare form of myocarditis, associated with a high mortality rate due to a high risk of sudden cardiac death. Lymphocytic myocarditis might present as a relevant extrapulmonary manifestation after coronavirus disease 2019 (COVID-19) infection. Case presentation. We report a case of a 26-year-old male with lymphocytic myocarditis, presenting with a 1-month history of increasing fatigue, palpitations, and shortness of breath. Eight weeks before, he was tested positive for SARS-CoV-2. He had received 2-dose schedule of the COVID-19 mRNA vaccine Comirnaty® (BioNTech/Pfizer) 6 months prior to his admission. Diagnostic work-up by echocardiography and cardiac magnetic resonance (CMR) imaging demonstrated a severely reduced left ventricular function and a strong midmyocardial late gadolinium enhancement (LGE). Histology and immunohistology of the endomyocardial biopsies revealed an acute lymphocytic myocarditis. Immunosuppressive therapy with a steroid taper in combination with azathioprine 300 mg/day was initiated. The patient was equipped with a LifeVest®. On day 17, a non-sustained ventricular tachycardia was documented. Follow-up CMR imaging after 3 months showed a slightly improved systolic left ventricular function, and a strong LGE was still detectable. Conclusions: The case highlights the significance of recognizing lymphocytic myocarditis correlated to COVID-19. It is important to be vigilant also of a later presentation of cardiomyopathy in patients diagnosed with COVID-19 due to high mortality without immediate support.

Global left ventricular load in asymptomatic aortic stenosis: covariates and prognostic implication (the SEAS trial).

INTRODUCTION: Valvuloarterial impedance (Zva) is a measure of global (combined valvular and arterial) load opposing left ventricular (LV) ejection in aortic stenosis (AS). The present study identified covariates and tested the prognostic significance of global LV load in patients with asymptomatic AS. METHODS: 1418 patients with mild-moderate, asymptomatic AS in the Simvastatin Ezetimibe in Aortic Stenosis (SEAS) study were followed for a mean of 43±14 months during randomized, placebo-controlled treatment with combined simvastatin 40 mg and ezetimibe 10 mg daily. High global LV load was defined as Zva >5 mm Hg/ml/m2. The impact of baseline global LV load on rate of major cardiovascular (CV) events, aortic valve events and total mortality was assessed in Cox regression models reporting hazard ratio (HR) and 95% Confidence Intervals (CI). RESULTS: High global LV load was found in 18% (n=252) of patients and associated with female gender, higher age, hypertension, more severe AS and lower ejection fraction (all p<0.05). A total of 476 major CV events, 444 aortic valve events and 132 deaths occurred during follow-up. In multivariate Cox regression analyses, high global LV load predicted higher rate of major CV events (HR 1.35 [95% CI 1.08-1.71], P=0.010) and aortic valve events (HR 1.41 [95% CI 1.12-1.79], P=0.004) independent of hypertension, LV ejection fraction, female gender, age, abnormal LV geometry and AS severity, but failed to predict mortality. CONCLUSION: In asymptomatic AS, assessment of global LV load adds complementary information on prognosis to that provided by hypertension or established prognosticators like AS severity and LV ejection fraction.

Grading of Aortic Stenosis: Is it More Complicated in Women?

Aortic stenosis (AS) is the most common valvular heart disease and the main indication for valvular replacement in older women. Correct AS grading is mandatory for an adequate selection of patients for both surgical and transcatheter aortic valve replacement. Women and men have different AS severity grades at the same level of aortic valve calcification. Moreover, besides having smaller cardiac volumes, left ventricular outflow tract and aortic size, women have a specific pattern of left ventricular structural and functional remodelling in response to the AS-related chronic pressure overload. Here, the sex-specific cardiac changes in AS that make AS grading more challenging in women, with consequences for the management and outcome of this group of patients, are reviewed.

New Evidence About Aortic Valve Stenosis and Cardiovascular Hemodynamics.

Aortic stenosis (AS) is the most common degenerative valvular disease in western word. In patients with severe AS, small changes in aortic valve area can lead to large changes in hemodynamics. The correct understanding of cardiac hemodynamics and its interaction with vascular function is of paramount importance for correct identification of severe AS and to plan effective strategies for its treatment. In the current review with highlight the importance of pressure recovery phenomenon and valvular arterial impedance as novel tools in the evaluation of patients with aortic stenosis.

Prognosis in asymptomatic patients with discordantly graded aortic valve stenosis based on pressure recovery adjusted valve area.

OBJECTIVE: We hypothesised that patients with asymptomatic aortic stenosis (AS) who remain with discordantly graded aortic valve stenosis (DGAS) after adjustment for pressure recovery in the aortic root represents a subgroup of patients with increased cardiovascular risk. METHODS: Data from 1353 patients with asymptomatic mild-moderate AS and preserved left ventricular ejection fraction enrolled in the Simvastatin and Ezetimibe in AS study was used. DGAS was identified as combined pressure adjusted valve area (energy loss) <1.0 cm² and mean aortic gradient<40 mm Hg (DGASEL). Outcome was assessed in Cox regression analysis and reported as HR and 95% CI. RESULTS: DGASEL was found in 196 (14.5%) patients at baseline, and was associated with older age, female sex, smaller aortic annulus diameter, lower heart rate, more extensive valve calcification and low flow (all p<0.05). In Cox regression analysis, DGASEL was associated with higher rate of heart failure (HF) hospitalisation (HR 3.31 (95% CI 1.54 to 7.09)), cardiovascular death (HR 2.63 (95% CI 1.34 to 5.17)) and all-cause mortality (HR 1.73 (95% CI 1.04 to 2.87)) independent of confounders including low flow and aortic valve calcification (all p<0.05). CONCLUSIONS: Patients with asymptomatic AS who remain with discordant grading after adjustment for pressure recovery have increased risk for HF and death. TRIAL REGISTRATION NUMBER: NCT00092677.

Impact of pressure recovery on the assessment of pulmonary homograft function using Doppler ultrasound.

Relevant pressure recovery (PR) has been shown to increase functional stenotic aortic valve orifice area and reduce left ventricular load. However, little is known about the relevance of PR in the pulmonary artery. The study examined the impact of PR using 2D-echocardiography in the pulmonary artery distal to the degenerated homograft in patients after Ross surgery. Ninety-two patients with pulmonary homograft were investigated by Doppler echocardiography (mean time interval after surgery 31 ± 26 months). PR was measured as a function of pulmonary artery diameter determined by computed tomography angiography. Homograft orifice area, valve resistance, and transvalvular stroke work were calculated with and without considering PR. PR decreased as the pulmonary artery diameter increased (r = -0.69, p < 0.001). Mean PR was 41.5 ± 7.1% of the Doppler-derived pressure gradient (Pmax ), which resulted in a markedly increased homograft orifice area (energy loss coefficient index [ELCOI] vs. effective orifice area index [EOAI], 1.3 ± 0.4 cm2 /m2 vs. 0.9 ± 0.4 cm2 /m2 , p < 0.001). PR significantly reduced homograft resistance and transvalvular stroke work (822 ± 433 vs. 349 ± 220 mmHg × ml, p < 0.0001). When PR was considered, the correlations of the parameters used were significantly better, and 11 of 18 patients (61%) in the group with severe homograft stenosis (EOAI <0.6 cm2 /m2 ) could be reclassified as moderate stenosis. Our results showed that the Doppler measurements overestimated the degree of homograft stenosis and thus the right ventricular load, when PR was neglected in the pulmonary artery. Therefore, Doppler measurements that ignore PR can misclassify homograft stenosis and may lead to premature surgery.

Aortic root geometry in aortic stenosis patients (a SEAS substudy).

AIMS: To report aortic root geometry by echocardiography in a large population of healthy, asymptomatic aortic stenosis (AS) patients in relation to current vendor-specified requirements for transcatheter aortic valve implantation (TAVI). METHODS AND RESULTS: Baseline data in 1481 patients with asymptomatic AS (mean age 67 years, 39% women) in the Simvastatin Ezetimibe in AS study were used. The inner aortic diameter was measured at four levels: annulus, sinus of Valsalva, sinotubular junction and supracoronary, and sinus height as the annulo-junctional distance. Analyses were based on vendor-specified requirements for the aortic root geometry for current available prostheses, CoreValve and Edwards-Sapien. The ratio of sinus of Valsalva height to sinus width was 1:2. In multivariate linear regression analysis, larger sinus of Valsalva height was associated with older age, larger sinus of Valsalva diameter, lower ejection fraction and smaller supracoronary diameter (multiple R(2) = 0.19, P< 0.01). The required annulus diameter for implantation of CoreValve was met in 61.9%, and for the Edwards-Sapien prosthesis in 66.9%. Overall, annular dimension feasible for TAVI using any available prosthesis was found in 78.2% of patients and in 77.7% of patients also the required minimum sinus of Valsalva height was found. Comparing the group of patients who met TAVI requirements to those who did not, the latter included more women and patients with lower body height and weight and significantly smaller aortic root diameters (all P < 0.05). CONCLUSION: Among AS patients in the SEAS study, 27% of women and 19% of men did not have aortic root geometry fulfilling current requirements for TAVI.

Higher Acceleration/Ejection Time Ratio Predicts Impaired Outcome in Aortic Valve Stenosis.

BACKGROUND: Acceleration time (AT)/ejection time (ET) ratio is a marker of aortic valve stenosis (AS) severity and predicts outcome in moderate-severe AS. METHODS: We explored the association of increased AT/ET ratio on prognosis in 1530 asymptomatic patients with presumably mild-moderate AS, normal ejection fraction, and without known diabetes or cardiovascular disease. Patients were part of the SEAS study (Simvastatin Ezetimibe Aortic Stenosis). Patients were grouped according to the optimal AT/ET ratio threshold to predict cardiovascular death and heart failure hospitalization. Low-gradient severe AS was identified as combined valve area ≤1.0 cm2 and mean gradient <40 mm Hg. Outcome was assessed in Cox regression analyses, and results are reported as hazard ratio and 95% CI. RESULTS: Higher AT/ET ratio was significantly associated with lower systolic blood pressure, lower left ventricular ejection fraction, lower stress-corrected midwall shortening, low flow, and with higher left ventricular mass and higher peak aortic jet velocity. AT/ET ratio ≥0.32 provided the optimal cutoff for predicting incident cardiovascular death and heart failure hospitalization in the total study sample. In patients with low-gradient severe AS, this threshold was >0.32. AT/ET ratio ≥0.32 had a 79% higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 1.79 [95% CI, 1.20-2.68]). In patients with low-gradient severe AS, AT/ET ratio >0.32 was associated with a 2-fold higher risk of cardiovascular death and heart failure hospitalization (hazard ratio, 2.15 [95% CI, 1.22-3.77]). CONCLUSIONS: In asymptomatic nonsevere AS and low-gradient severe AS, higher AT/ET ratio was associated with increased cardiovascular morbidity and mortality. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00092677.

Low myocardial energetic efficiency is associated with increased mortality in aortic stenosis.

OBJECTIVES: In hypertension, low myocardial energetic efficiency (MEEi) has been documented as an integrated marker of metabolic and left ventricular (LV) myocardial dysfunction. We tested the predictive performance of MEEi in initially asymptomatic aortic stenosis (AS) patients free from diabetes and known cardiovascular disease. METHODS: Data from 1703 patients with mostly moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study followed for 4.3 years was used. MEE was calculated from Doppler stroke volume/([heart rate/60]) and indexed to LV mass (MEEi). The threshold value for MEEi associated with increased mortality was identified in generalised additive model with smoothing splines. Covariables of MEEi were identified in logistic regression analysis. Outcome was assessed in Cox regression analysis and reported as HR and 95% CI. RESULTS: MEEi <0.34 mL/s per gram was associated with increased cardiovascular mortality (n=80) (HR 2.53 (95% CI 1.50 to 4.28)) and all-cause mortality (n=155) (HR 1.74 (95% CI 1.20 to 2.52)) (both p<0.01). The association was independent of confounders of low MEEI (<0.34 mL/s per gram) identified in multivariable logistic regression analysis, including more severe AS, higher body mass index, lower LV midwall shortening and ejection fraction and presence of hypertension. Comparison of the Cox models with and without MEEi among the covariables demonstrated that MEEi significantly improved the prognostic yield (both p<0.01). CONCLUSIONS: In patients with initially asymptomatic AS, low MEEi was associated with clustering of cardiometabolic risk factors, lower LV myocardial function and subsequent increased mortality during 4.3 years follow-up, independent of known prognosticators. TRIAL REGISTRATION NUMBER: NCT00092677.

Cardiac Arrest and Successful Extracorporeal Cardiopulmonary Resuscitation as a Result of a Refeeding Syndrome in a Young Female with Anorexia Nervosa.

Anorexia nervosa is a potentially life-threatening eating disorder, characterized by an abnormally low body weight. This case report illustrates a 22-year old female with cardiac arrest due to a refeeding syndrome in a patient with anorexia nervosa. It features the successful use of extracorporeal cardiopulmonary resuscitation in a case of severe left ventricular dysfunction resulting in a favorable outcome. Conclusion. We present the first case of a cardiac arrest due to a refeeding syndrome in anorexia nervosa featuring the successful use of an extracorporeal cardiopulmonary resuscitation approach as a bridge to full recovery.

Electrical storm in Brugada syndrome successfully treated with orciprenaline; effect of low-dose quinidine on the electrocardiogram.

We report a case of an electrical storm occurring in a patient implanted with a cardioverter defibrillator for symptomatic Brugada syndrome. Recurrent ventricular fibrillation was initiated by short-coupled premature ventricular beats of right ventricular origin, associated with a fixed Brugada type 2 electrocardiographic pattern. Low-dose orciprenaline application as an intravenous bolus followed by an infusion inhibited the recurrence of ventricular fibrillation and normalized the electrocardiographic pattern. Low-dose oral quinidine had only a moderate effect on the ST-elevation.

Strain rate imaging for functional quantification of the left atrium: atrial deformation predicts the maintenance of sinus rhythm after catheter ablation of atrial fibrillation.

AIMS: The aim of the study was to investigate the atrial myocardial deformation properties using ultrasound strain rate (SR) imaging in patients after catheter ablation of atrial fibrillation (AF) and to compare its prognostic value in maintaining sinus rhythm. METHODS AND RESULTS: A total of 118 patients with AF (74 paroxysmal AF, 44 persistent AF) underwent transthoracic echocardiography with Doppler-derived SR examinations before and after ablation as well as during 3 months of follow-up (FU). Peak SR and strain (S) were measured at each left atrium (LA) segment (septal, lateral, anterior, inferior) during systole (LAs) and at early (LAe) and late diastole (LAa). Clinical and echocardiographic parameters of patients with maintained sinus rhythm during FU were compared with those with recurrent AF and controls (n = 25 patients). Of 118 patients 82 (69%) showed stable sinus rhythm during FU. Atrial myocardial properties after catheter ablation differed significantly in patients with paroxysmal AF (SR-LAs 2.5 s(-1), S-LAs 30%, SR-LAa -2.2 s(-1)) from patients with persistent AF (SR-LAs 2.3 s(-1), S-LAs 25%, SR-LAa -1.9 s(-1)) and controls (SR-LAs 4.1 s(-1), S-LAs 88%, SR-LAa -2.9 s(-1)) (P = 0.011). Best individual predictors of sinus rhythm maintenance were cut-off values of >2.25 s(-1) for septal and inferior SR-LAs and of >19.5% for inferior S-LAs (P < 0.001). LA deformation properties increased in patients with maintained sinus rhythm during FU in contrast to patients with recurrent AF (P = 0.001). CONCLUSION: SR imaging enables the quantitative assessment of the LA function and can be considered as a potential marker of atrial reverse remodelling. Patients with higher atrial S and SR after catheter ablation appear to have a greater likelihood of maintenance of sinus rhythm. This may have further implications for the anticoagulation regime and the risk of cardioembolic complications.

Low systemic arterial compliance is associated with increased cardiovascular morbidity and mortality in aortic valve stenosis.

OBJECTIVE: Lower systemic arterial compliance (SAC) is associated with increased cardiovascular morbidity and mortality in hypertension, but this has not been assessed in a prospective study in aortic valve stenosis (AS). METHODS: Data from 1641 patients (38% women) with initially asymptomatic mild-moderate AS enrolled in the Simvastatin and Ezetimibe in Aortic Stenosis study was used. Median follow-up was 4.3 years. SAC was assessed from Doppler stroke volume index to central pulse pressure ratio and considered low if ≤0.64 mL/m², corresponding to the lower tertile in the population. The association of SAC with outcome was assessed in Cox regression analysis and reported as HR and 95% CI. RESULTS: Low SAC at baseline was characterised by older age, female sex, hypertension, obesity, presence of a small aortic root, lower mean aortic gradient and more severe AS by effective aortic valve area (all p<0.01). In Cox regression analysis adjusting for factors, low SAC was associated with higher HRs for cardiovascular death (HR 2.13(95% CI 1.34 to 3.40) and all-cause mortality (HR 1.71(95% CI 1.23 to 2.38)), both p=0.001). The results did not change when systolic or diastolic blood pressure, other measures of AS severity or presence of discordantly graded AS were included in subsequent models. Presence of low SAC did not improve mortality prediction in reclassification analysis. CONCLUSIONS: In patients with AS without diabetes and known cardiovascular disease, but a high prevalence of hypertension, low SAC was associated with higher cardiovascular and all-cause mortality independent of well-known prognosticators. TRIAL REGISTRATION NUMBER: NCT00092677; Post-results.

Higher left ventricular mass-wall stress-heart rate product and outcome in aortic valve stenosis.

OBJECTIVE: Whether increased myocardial oxygen demand could help explain the association of left ventricular (LV) hypertrophy with higher adverse event rate in patients with aortic valve stenosis (AS) is unknown. METHODS: Data from 1522 patients with asymptomatic mostly moderate AS participating in the Simvastatin-Ezetimibe in AS study followed for a median of 4.3 years was used. High LV mass-wall stress-heart rate product was identified as >upper 95% CI limit in normal subjects. The association of higher LV mass-wall stress-heart rate product with major cardiovascular (CV) events, combined CV death and hospitalised heart failure and all-cause mortality was tested in Cox regression analyses, and reported as HR and 95% CI. RESULTS: High LV mass-wall stress-heart rate product was found in 19% at baseline, and associated with male sex, higher body mass index, hypertension, LV hypertrophy, more severe AS and lower LV ejection fraction (all p<0.01). Adjusting for these confounders in time-varying Cox regression analysis, 1 SD higher LV mass-wall stress-heart rate product was associated with higher HR of major CV events (HR 1.16(95% CI 1.06 to 1.29)), combined CV death and hospitalised heart failure (HR 1.29(95% CI 1.09 to 1.54)) and all-cause mortality (HR 1.34(95% CI 1.13 to 1.58), all p<0.01). CONCLUSION: In patients with initially mild-moderate AS, higher LV mass-wall stress-heart rate product was associated with higher mortality and heart failure hospitalisation. Our results suggest that higher myocardial oxygen demand is contributing to the higher adverse event rate reported in AS patients with LV hypertrophy. TRIAL REGISTRATION NUMBER: NCT000092677;Post-results.

Assessment of the German and Italian Stress Cardiomyopathy Score for Risk Stratification for In-hospital Complications in Patients With Takotsubo Syndrome.

Importance: Takotsubo syndrome (TTS) is an acute, reversible heart failure syndrome featured by significant rates of in-hospital complications. There is a lack of data for risk stratification during hospitalization. Objective: To derive a simple clinical score for risk prediction of in-hospital complications among patients with TTS. Design, Setting, and Participants: In this prognostic study, 1007 consecutive patients were enrolled in the German and Italian Stress Cardiomyopathy (GEIST) registry from July 1, 2007, through December 31, 2017, and identified as the derivation cohort; 946 patients were enrolled in the Spanish Registry for Takotsubo Cardiomyopathy (RETAKO) as the external score validation. An admission risk score was developed using a stepwise multivariable regression analysis from 2 registries. Data analysis was performed from March 1, 2018, through July 31, 2018. Main Outcomes and Measures: In-hospital complications were defined as death, pulmonary edema, need for invasive ventilation, and cardiogenic shock. Four variables were identified as independent predictors of in-hospital complications and were used for the score: male sex, history of neurologic disorder, right ventricular involvement, and left ventricular ejection fraction (LVEF). Results: Of the 1007 patients enrolled in the GEIST registry, 107 (10.6%) were male, with mean (SD) age of 69.8 (11.4) years. Overall rate of in-hospital complications was 23.3% (235 of 1007) (death, 4.0%; pulmonary edema, 5.8%; invasive ventilation, 6.4%; and cardiogenic shock, 9.1%). The GEIST prognosis score was derived by providing 20 points each for male sex and history of neurologic disorders and 30 points for right ventricular involvement and then subtracting the value in percent of LVEF (decimal values between 0.15 and 0.70). Score accuracy on area under the receiver operating characteristic curve analysis was 0.71, with a negative predictive power of 87% with scores less than 20. External validation in the RETAKO population (124 [13.1%] male; mean [SD] age, 69.5 [14.9] years) revealed an area under the curve of 0.73 (P = .46 vs GEIST derivation cohort). Stratification into 3 risk groups (<20, 20-40, and >40 points) classified 316 patients (40.9%) as having low risk; 342 (44.3%) as having intermediate risk, and 114 (14.8%) as having high risk of complications. The observed in-hospital complication rates were 12.7% for low-risk patients, 23.4% for intermediate-risk patients, and 58.8% for high-risk patients (P < .001 for trend). After 2.6 years of follow-up, patients with in-hospital complications had significantly higher rates of mortality than those without complications (40% vs 10%, P = .01). Conclusions and Relevance: The GEIST prognostic score may be useful in early risk stratification for TTS. High-risk patients with TTS may require an intensive care unit stay, and low-risk patients with TTS could be discharged within a few days. In-hospital complications in patients with TTS may be associated with increased risk of long-term mortality.