Von Willebrand Factor Multimers during Transcatheter Aortic-Valve Replacement.

BACKGROUND: Postprocedural aortic regurgitation occurs in 10 to 20% of patients undergoing transcatheter aortic-valve replacement (TAVR) for aortic stenosis. We hypothesized that assessment of defects in high-molecular-weight (HMW) multimers of von Willebrand factor or point-of-care assessment of hemostasis could be used to monitor aortic regurgitation during TAVR. METHODS: We enrolled 183 patients undergoing TAVR. Patients with aortic regurgitation after the initial implantation, as identified by means of transesophageal echocardiography, underwent additional balloon dilation to correct aortic regurgitation. HMW multimers and the closure time with adenosine diphosphate (CT-ADP), a point-of-care measure of hemostasis, were assessed at baseline and 5 minutes after each step of the procedure. Mortality was evaluated at 1 year. A second cohort (201 patients) was studied to validate the use of CT-ADP in order to identify patients with aortic regurgitation. RESULTS: After the initial implantation, HMW multimers normalized in patients without aortic regurgitation (137 patients). Among the 46 patients with aortic regurgitation, normalization occurred in 20 patients in whom additional balloon dilation was successful but did not occur in the 26 patients with persistent aortic regurgitation. A similar sequence of changes was observed with CT-ADP. A CT-ADP value of more than 180 seconds had sensitivity, specificity, and negative predictive value of 92.3%, 92.4%, and 98.6%, respectively, for aortic regurgitation, with similar results in the validation cohort. Multivariable analyses showed that the values for HMW multimers and CT-ADP at the end of TAVR were each associated with mortality at 1 year. CONCLUSIONS: The presence of HMW-multimer defects and a high value for a point-of-care hemostatic test, the CT-ADP, were each predictive of the presence of aortic regurgitation after TAVR and were associated with higher mortality 1 year after the procedure. (Funded by Lille 2 University and others; ClinicalTrials.gov number, NCT02628509.).

Single high-dose erythropoietin administration immediately after reperfusion in patients with ST-segment elevation myocardial infarction: results of the erythropoietin in myocardial infarction trial.

BACKGROUND: Preclinical studies and pilot clinical trials have shown that high-dose erythropoietin (EPO) reduces infarct size in acute myocardial infarction. We investigated whether a single high-dose of EPO administered immediately after reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) would limit infarct size. METHODS: A total of 110 patients undergoing successful primary coronary intervention for a first STEMI was randomized to receive standard care either alone (n = 57) or combined with intravenous administration of 1,000 U/kg of epoetin ß immediately after reperfusion (n = 53). The primary end point was infarct size assessed by gadolinium-enhanced cardiac magnetic resonance after 3 months. Secondary end points included left ventricular (LV) volume and function at 5-day and 3-month follow-up, incidence of microvascular obstruction (MVO), and safety. RESULTS: Erythropoietin significantly decreased the incidence of MVO (43.4% vs 65.3% in the control group, P = .03) and reduced LV volume, mass, and function impairment at 5-day follow-up (all P < .05). After 3 months, median infarct size (interquartile range) was 17.5 g (7.6-26.1 g) in the EPO group and 16.0 g (9.4-28.2 g) in the control group (P = .64); LV mass, volume, and function were not significantly different between the 2 groups. The same number of major adverse cardiac events occurred in both groups. CONCLUSIONS: Single high-dose EPO administered immediately after successful reperfusion in patients with STEMI did not reduce infarct size at 3-month follow-up. However, this regimen decreased the incidence of MVO and was associated with transient favorable effects on LV volume and function.

Prognostic value of hemoglobin decline over the GRACE score in patients hospitalized for an acute coronary syndrome.

In this work, we analyzed the prognostic significance of changes in hemoglobin during intensive care unit (ICU) stay in patients with acute coronary syndromes (ACS). We prospectively enrolled 591 patients (62 ± 14 years old, 73% male, 48% ST elevated myocardial infarction) free of blood cell transfusion or bleeding events. Changes in hemoglobin between admission and ICU discharge were obtained. The primary endpoint was death or hospitalization for MI within 6 months. Hemoglobin decreased from 13.65 ± 1.77 to 13.17 ± 1.74 g/dl, p < 0.0001 in the whole population. The end point was reached in 43 patients at a mean follow-up of 180 (range 2-180 days). A decrease in hemoglobin ≥0.9 g/dl (32% of the population) was associated with adverse clinical outcomes (HR 2.37, 95% CI (1.30-4.35), p = 0.005, respectively). In multivariate analysis, age >77 year-old (p = 0.0016), Killip class ≥2 (p = 0.009), anemia (p = 0.0064), decreased estimated glomerular filtration rate (p = 0.003), and hemoglobin decline ≥0.9 g/dl (p < 0.0001) were independently associated with outcome. Hemoglobin decline and anemia both provided additional prognostic information on top of the GRACE score, as demonstrated by a systematic improvement in model global fit, discrimination, and calibration. Hemoglobin decline is frequent during ICU stay in non-bleeding ACS patients. A decline in hemoglobin ≥0.9 g/dl identifies high-risk patients. Identification of these patients refines the prognostic value of the GRACE score.

Addition of B-type natriuretic peptide to the GRACE score to predict outcome in acute coronary syndrome: a retrospective (development) and prospective (validation) cohort-based study.

AIMS: The present study was designed to build and validate a composite score based on the Global Registry of Acute Coronary Events (GRACE) score and B-type natriuretic peptide (BNP) concentrations to predict outcome in patients with acute coronary syndromes (ACS). METHODS: The GRACE risk score and BNP concentrations were obtained in a retrospective and a prospective cohort. A composite score including the GRACE score and BNP concentrations was first developed in a retrospective cohort of 248 patients with ACS and then validated in a prospective cohort of 575 patients. The primary outcome was 6-month death or myocardial infarction. RESULTS: End points were reached in 34 patients in the retrospective cohort and in 68 patients in the prospective cohort. Both higher BNP concentration and GRACE score were independently associated with outcome in the retrospective cohort (p=0.003 and p<0.0001). The composite score could be obtained as follows: GRACE+BNP/60. The use of the composite score increased the accuracy of the GRACE score, with an increase in the C statistic from 0.810 (0.727 to 0.892) to 0.822 (0.745 to 0.902) in the retrospective cohort and from 0.724 (0.657 to 0.791) to 0.750 (0.686 to 0.813) in the prospective cohort. Finally, 7% of patients in the prospective study population were reclassified from low to high risk or from high to low risk using this composite score. CONCLUSIONS: Plasma BNP levels refine the accuracy of the GRACE score. A comprehensive risk score, which includes BNP concentration and the GRACE risk score, might improve ACS risk stratification in clinical practice.

Prognostic importance of comorbidities in heart failure with preserved left ventricular ejection fraction.

The relative impact of comorbidities and parameters of left ventricular diastolic function on clinical outcome has not been thoroughly investigated in patients who are hospitalized for heart failure decompensation and found to have preserved ejection fraction. We identified 98 HFpEF patients among 1452 patients admitted with acute heart failure. Clinical characteristics, hemoglobin levels, estimated glomerular filtration rate (eGFR), B-type natriuretic peptide (BNP) and Doppler-echocardiographic parameters were analyzed. The primary end point of the study combined death and rehospitalization for decompensated heart failure after the index hospitalization. Mean age was 76 ± 9 years. LV ejection fraction, E/E (a) ratio, and estimated systolic pulmonary artery pressure were 61 (55-67)%, 12.9 (9.4-15.1), 40 (32-46) mmHg, respectively. BNP values, hemoglobin and eGFR were 287 (164-562) pg/mL, 11.3 (10.4-12.4) g/dL and 45 (37-74) mL/min/m(2), respectively. During a mean follow-up of 17 ± 11 months, 56% reached the primary endpoint of the study: 31 died and 24 were re-hospitalised for heart failure. Diabetes [HR = 1.76 (1.03-3.00), P = 0.039], lower systolic blood pressure [HR = 0.99 (0.97-0.99), P = 0.016], hemoglobin [HR = 0.62 (0.49-0.76), P < 0.0001], and eGFR [HR = 0.98 (0.97-0.99), P = 0.004] were associated with a poor outcome. Neither BNP nor echocardiographic parameters were correlated with outcome. Comorbidities primarily correlate with outcome in patients with HFpEF.

Myocardial Infarction incidence during national lockdown in two French provinces unevenly affected by COVID-19 outbreak: An observational study.

BACKGROUND: A reduction of admission for MI has been reported in most countries affected by COVID-19. No clear explanation has been provided. METHODS: To report the incidence of myocardial infarction (MI) admission during COVID-19 pandemic and in particular during national lockdown in two unequally affected French provinces (10-million inhabitants) with a different media strategy, and to describe the magnitude of MI incidence changes relative to the incidence of COVID-19-related deaths. A longitudinal study to collect all MIs from January 1 until May 17, 2020 (study period) and from the identical time period in 2019 (control period) was conducted in all centers with PCI-facilities in northern "Hauts-de-France" province and western "Pays-de-la-Loire" Province. The incidence of COVID-19 fatalities was also collected. FINDINGS: In "Hauts-de-France", during lockdown (March 18-May 10), 1500 COVID-19-related deaths were observed. A 23% decrease in MI-IR (IRR=0.77;95%CI:0.71-0.84, p<0.001) was observed for a loss of 272 MIs (95%CI:-363,-181), representing 18% of COVID-19-related deaths. In "Pays-de-la-Loire", 382 COVID-19-related deaths were observed. A 19% decrease in MI-IR (IRR=0.81; 95%CI=0.73-0.90, p<0.001) was observed for a loss of 138 MIs (95%CI:-210,-66), representing 36% of COVID-19-related deaths. While in "Hauts-de-France" the MI decline started before lockdown and recovered 3 weeks before its end, in "Pays-de-la-Loire", it started after lockdown and recovered only by its end. In-hospital mortality of MI patients was increased during lockdown in both provinces (5.0% vs 3.4%, p=0.02). INTERPRETATION: It highlights one of the potential collateral damages of COVID-19 outbreak on cardiovascular health with a dramatic reduction of MI incidence. It advocates for a careful and weighted communication strategy in pandemic crises. FUNDING: The study was conducted without external funding.

Atrial septal defect associated with dilated cardiomyopathy in the setting of acute cardiac failure: importance of comprehensive bedside echocardiography in ICU.

The current report describes two patients with severe heart failure due to dilated cardiomyopathy in whom discrepancy between thermodilution cardiac output and clinical status was due to left-to-right shunt. Misdiagnosis of shunting was harmful in the early management of the first case. Secundum type atrial septal defect was confirmed by pathology in both cases. Blood samples for oxymetry should be routinely drawn during right heart catheterization for screening for intracardiac shunts. Using bedside echocardiography pulmonary-to-systemic flow ratio should also be systematically evaluated in the setting of right ventricular dilation.

Pivotal role of bedside Doppler echocardiography in the assessment of patients with acute heart failure and mitral regurgitation.

Patients presenting with mitral regurgitation and acute heart failure remain a challenge for the clinicians. Bedside echocardiography ascertains the functional or primary nature of mitral regurgitation, thereby allowing to focus therapy on the left ventricle and mitral valve apparatus in patients with functional mitral regurgitation and to hasten mitral valve repair or replacement when acute heart failure results from primary mitral regurgitation. This short article reviews the evaluation by bedside echocardiography to guide management of these patients.

Left ventricular abnormal response during dynamic exercise in patients with heart failure and preserved left ventricular ejection fraction at rest.

BACKGROUND: The mechanisms that contribute to limit functional capacity are incompletely understood in patients with preserved resting ejection fraction (HFpREF). We assessed left ventricular (LV) systolic response to dynamic exercise in patients with HFpREF and in patients with similar comorbidities to HFpREF patients but without history or evidence of heart failure. METHODS AND RESULTS: Twenty-five HFpREF patients in steady-state clinical condition without significant coronary artery disease and 25 hypertensive controls underwent exercise echocardiography. At rest, systolic pulmonary artery pressure, left atrial area, E/A and E/e' ratios were greater in patients with HFpREF than in control patients, whereas peak systolic mitral annular velocity was lower in HFpREF patients. The exercise-induced changes in LVEF, forward stroke volume, and cardiac output were significantly lower in HFpREF compared with control patients (-4 +/- 8 vs. +6 +/- 6 %, P = .001; -4 +/- 9 vs. +10 +/- 10 mL, P < .0001, and 1.6 +/- 1.2 vs. 3.5 +/- 1.8 L/min, P < .0001, respectively). Exercise-induced changes in effective arterial elastance significantly differed in HFpREF and control patients (0.5 +/- 0.6 vs. -0.2 +/- 0.5 mm Hg/mL, P < .0001). In addition, 7 of the 25 HFpREF patients developed functional mitral regurgitation during exercise and none in controls. CONCLUSIONS: When compared with patients with similar comorbidities but without history or evidence of heart failure, patients with HFpREF experience greater arterial stiffening and thereby a deterioration of global LV systolic performance during dynamic exercise.

Septic pseudo-aneurysm of the left main trunk in a dialysis patient.

This case report relating the association between a septic pseudo-aneurysm of the left trunk and myocardial infarction underscores the importance of early non-invasive imaging when acute myocardial infarction is associated with frank clinical or biological signs of systemic sepsis.

Prognostic importance of tissue Doppler-derived diastolic function in patients presenting with acute coronary syndrome: a bedside echocardiographic study.

AIMS: We sought to evaluate the prognostic value of bedside tissue Doppler derived diastolic function in patients presenting with acute coronary syndrome (ACS) on top of major clinical predictors of mortality and routine laboratory testings. METHODS AND RESULTS: Bedside Doppler echocardiography and laboratory tests were prospectively performed in 239 consecutive patients (mean age 62 +/- 14, 69% men) admitted for ACS. Ratio of early transmitral flow (E) to early mitral annulus velocities (e') was calculated. The study endpoint was cardiac death. The median follow-up period was 2 years. E/e' was >15 in 39 patients. Multivariate predictors of E/e' > 15 were older age, diabetes, non-ST-segment elevation ACS, and decreased LV ejection fraction (LVEF). Survival free from cardiac death was lower in patients with E/e' ratio >15 (P = 0.01). History of coronary artery disease, lower creatinine clearance, higher glycemia on admission, decreased LVEF, and E/e' >15 were independent predictors of cardiac death. CONCLUSION: Bedside Doppler echocardiography provides prognostic information on top of major clinical predictors of mortality and routine laboratory testings in patients presenting with ACS.

[What is the place of beta-adrenergic blockade therapy in coronary syndromes in the modern management era?]. / Bêta-bloquants et syndromes coronariens: les réponses d'hier s'appliquent-elles aux stratégies d'aujourd'hui?

This paper shows the eventual benefits of treatment with beta-blockers in post-myocardial infarction. An overview of main clinical trials that have been conducted to test this therapeutic in acute coronary syndrome. In patients presenting with acute myocardial infarction, the early use of intravenous beta-blockers had shown a modest and non significant reduction in mortality. Substantial reductions in mortality and reinfarction have been demonstrated when beta-blockers have been used soon after an acute myocardial infarction and continued long-term. However, these benefits were observed in randomised clinical trials conducted in the 1970s and 1980s, prior to the widespread use of reperfusion therapies and antiplatelet agents. It appears obvious that the long-term use of beta-blockers may be questionable after any acute coronary syndrome especially if complete reperfusion has been achieved and left ventricular function is preserved.

[Is there a role for calcium antagonists when beta-adrenergic blockade therapy is contraindicated in post-myocardial infarction?]. / Quelle est la place des inhibiteurs calciques lorsque les bêta-bloquants sont contre-indiqués dans le traitement du post-infarctus du myocarde?

The purpose of this paper is to examine the eventual benefits of treatment with calcium channel blockers in post-myocardial infarction, through an overview of main placebo-controlled trials that have been conducted to test this therapeutic in acute coronary syndromes. It appears obvious that the vast majority of these trials was conducted in the pre-reperfusion era and failed to demonstrate a reduction in mortality. To conclude, the superiority of a therapy with calcium antagonists over a placebo in the management of post-myocardial infarction remains unknown. In contrast, adverse effects associated with the prescription of calcium antagonists are well known.

[Not Available]. / Quelle est la place des inhibiteurs calciques lorsque les bêta-bloquants sont contre-indiqués dans le traitement du post-infarctus du myocarde ?

The purpose of this paper is to examine the eventual benefits of treatment with calcium channel blockers in post-myocardial infarction, through an overview of main placebo-controlled trials that have been conducted to test this therapeutic in acute coronary syndromes. It appears obvious that the vast majority of these trials was conducted in the pre-reperfusion era and failed to demonstrate a reduction in mortality. To conclude, the superiority of a therapy with calcium antagonists over a placebo in the management of post-myocardial infarction remains unknown. In contrast, adverse effects associated with the prescription of calcium antagonists are well known.

Acute heart failure due to transient left ventricular dyssynchrony: case study.

This case study describes an unusual cause of acute heart failure that resolved with early beta-blockade therapy. A 52-year-old woman who had acute heart failure with severe left ventricular systolic dysfunction and left bundle branch block was admitted to a university medical center. Contrast-enhanced magnetic resonance images of the heart did not show any evidence of myocardial infarction or myocarditis. Rate-related left bundle branch block and subsequent left ventricular dyssynchrony resulted in acute systolic dysfunction that resolved with beta-blockade therapy that allowed heart rate control and narrowing of the QRS complex. Of note, the use of inotropic agents would have dramatically worsened the cardiac condition.

Functional decline in elderly patients presenting with acute coronary syndromes: impact on midterm outcome.

BACKGROUND: Elderly patients with an acute coronary syndrome (ACS) are less likely to be enrolled into randomized, controlled trials or receive guideline-recommended therapies, because of a higher burden of comorbidity, including functional decline. AIM: To assess the prognostic value of functional decline in a prospective, observational cohort of elderly ACS patients. METHODS: ACS patients aged > or = 70 years were enrolled. The ACS definition included ST- and non-ST-segment elevation myocardial infarction, and unstable angina pectoris. Clinical admission and laboratory data and echocardiographic variables were recorded. Functional decline was defined as needing assisted care in daily life. The study endpoint was all-cause mortality. RESULTS: Overall, 151 patients were enrolled (mean age 78 + or - 5 years; 52% men). Twenty-eight (19%) patients had functional decline. No significant difference in therapeutic management was observed between patients with functional decline and those living independently. Twenty-seven (18%) patients died during follow-up (median 447 days). Functional decline correlated with poor outcome (p = 0.008; hazard ratio [HR] 2.87 [1.31-6.25]). Other prognostic markers were diabetes, Killip class > or = II, elevated E/Ea ratio, C-reactive protein, B-type natriuretic peptide, haemoglobin, glycaemia and no coronary angiography. By multivariable analysis, C-reactive protein >13 mg/L correlated with poor outcome (p = 0.007; HR 4.77 [1.52-14.96]). There was a trend towards correlation between functional decline and poor outcome (p = 0.051; HR = 2.77 [0.99-7.72]). CONCLUSION: Functional decline seems to portend poor prognosis in elderly ACS patients. Larger, community-based studies are needed to confirm these findings in a multivariable model.

Hemidiaphragmatic paralysis: an underestimated etiology of right-to-left shunt through patent foramen ovale?

OBJECTIVE: To report a specific pathophysiology of hemidiaphragmatic paralysis that may result in severe hypoxemia. DESIGN: Case series. SETTING: Intensive care unit in a cardiology hospital. PATIENTS: The series included three patients with refractory hypoxemia in whom a diagnosis of right-to-left-shunt through a patent foramen ovale was made by contrast echocardiography. The three patients had a complete right hemidiaphragmatic paralysis. INTERVENTION: Permanent percutaneous closure of the patent foramen ovale was successfully proceeded in all cases. MAIN RESULT: These procedures resulted in complete normalization of arterial oxygen saturation. CONCLUSION: To our knowledge, only three previous reports have described the association of right-to-left shunt through a patent foramen ovale and hemidiaphragmatic paralysis. Such association may be underestimated.

Momentarily stuck in the foramen ovale.

An 80-year-old woman was admitted for a diagnosis of severe pulmonary embolism. A large serpentine thrombus stuck in a patent foramen ovale (PFO) completely resolved without the patient experiencing any manifestation. The right renal artery was the final destination. Thromboaspiration was unsuccessful. Three months later, the patient was diagnosed with a malignant melanoma and metastatic dissemination.

Mid-ventricular ballooning heart syndrome.

Stress cardiomyopathies have been increasingly reported these last years, especially in women as a transient left ventricular apical ballooning syndrome. We report six cases in whom, in the context of anxious situations, echocardiograms and ventriculographies revealed mid-ventricular akinesis with preservation of apical and basal contractilities with normal coronary arteriography. This "mid-ventricular ballooning heart syndrome " should probably be classified as a new type of heart stress related syndrome.

Transient left ventricular basal dysfunction without coronary stenosis in acute cerebral disorders: a novel heart syndrome (inverted Takotsubo).

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. We report 4 cases where, in the context of acute cerebral disorder, the echocardiograms revealed an extensive left ventricular circumferential akinesis except at the apex. Besides, for three of those cases no coronary disease has been highlighted. Recognition of such a pattern of LV dysfunction should lead to the search for an acute cerebral disease.