Endovascular closure of patent foramen ovale: a critical appraisal of published trials.

OBJECTIVE: The treatment of cryptogenic stroke patients with a patent foramen ovale (PFO) is controversial. A critical review of these studies is presented. METHODS: A description of all trials comparing medical and endovascular treatment with closing devices is given. Additional pertinent studies are discussed to help construct a rational basis for treatment decisions. RESULTS: Initial negative trials evaluating PFO closure were followed by positive studies published in 2017 and 2018. All trials evaluated young patients (up to 60 years). Methodological problems are present in all trials including their open label construction. Most positive trials developed strategies to increase the percentage of patients with interatrial septal aneurysms or hypermobility and large right-to-left shunts. Even in these positive trials, large numbers of patients need to be treated to avoid one stroke. Atrial fibrillation occurred in 2-6% and other adverse effects related to the procedure and to the devices occurred in a substantial number of patients. Incomplete occlusion of the PFO is also frequent. Anticoagulant treatment has not been adequately studied as a therapeutic option. CONCLUSION: Young patients with cryptogenic strokes seem to benefit from endovascular closure of a PFO in the presence of a large right-to-left shunt or an associated atrial septum aneurysm. For most other patients, a highly-individualized decision must be made, taking into account the low risk of recurrence in patients with a cryptogenic stroke attributable to a PFO, the high numbers needed to treat and the risks related to the procedure.

Endovascular closure of patent foramen ovale: a critical appraisal of published trials / Fechamento endovascular do forame oval patente: análise crítica dos estudos publicados

ABSTRACT The treatment of cryptogenic stroke patients with a patent foramen ovale (PFO) is controversial. A critical review of these studies is presented. Methods A description of all trials comparing medical and endovascular treatment with closing devices is given. Additional pertinent studies are discussed to help construct a rational basis for treatment decisions. Results Initial negative trials evaluating PFO closure were followed by positive studies published in 2017 and 2018. All trials evaluated young patients (up to 60 years). Methodological problems are present in all trials including their open label construction. Most positive trials developed strategies to increase the percentage of patients with interatrial septal aneurysms or hypermobility and large right-to-left shunts. Even in these positive trials, large numbers of patients need to be treated to avoid one stroke. Atrial fibrillation occurred in 2-6% and other adverse effects related to the procedure and to the devices occurred in a substantial number of patients. Incomplete occlusion of the PFO is also frequent. Anticoagulant treatment has not been adequately studied as a therapeutic option. Conclusion Young patients with cryptogenic strokes seem to benefit from endovascular closure of a PFO in the presence of a large right-to-left shunt or an associated atrial septum aneurysm. For most other patients, a highly-individualized decision must be made, taking into account the low risk of recurrence in patients with a cryptogenic stroke attributable to a PFO, the high numbers needed to treat and the risks related to the procedure.

RESUMO O tratamento de pacientes com infarto cerebral criptogênico e forame oval patente (FOP) é controverso. Uma revisão crítica destes estudos é apresentada. Métodos São descritos em detalhes os estudos comparando tratamento médico com o uso de próteses de oclusão do FOP após infarto cerebral. Discutem-se outros estudos pertinentes para ajudar na tomada racional de decisões terapêuticas individualizadas. Resultados Estudos iniciais avaliando fechamento endovascular com próteses foram negativos, porém seguidos de outros estudos com resultados positivos em 2017 e 2018. Somente pacientes até 60 anos foram estudados. Os estudos apresentam vários problemas metodológicos, incluindo sua natureza aberta. A maioria dos estudos positivos desenvolveu estratégias para aumentar o percentual de pacientes com risco aumentado de recorrência, especificamente grandes shunts direita-esquerda e aneurismas/hipermobilidade do septo interatrial. Mesmo estes estudos positivos revelaram um alto NNT (número de pacientes tratados para evitar um evento de desfecho). Fibrilação atrial ocorreu em 2-6 % dos pacientes tratados. Outras complicações relacionadas ao procedimento e às endopróteses e ainda fechamento incompleto do FOP foram também frequentes. Anticoagulantes poderiam constituir estratégia alternativa de tratamento clínico, mas não foram adequadamente estudados. Conclusão Pacientes jovens com infartos criptogênicos parecem beneficiar-se de oclusão endovascular do FOP na presença de grandes shunts e principalmente aneurismas ou hipermobilidade de septo interatrial. Para a maioria dos outros pacientes, uma decisão altamente individualizada deve ser tomada, considerando o baixo risco de recorrência dos infartos atribuíveis ao FOP, o ato NNT e os riscos inerentes ao procedimento.

Use of a sandwich technique to repair a left ventricular rupture after mitral valve replacement.

One difficulty with external repair of left ventricular rupture after mitral valve replacement is collateral bleeding in friable myocardium adjacent to the rupture. The bleeding is caused by tension on the closing sutures, whether or not pledgets have been used. We report the case of a 69-year-old woman who underwent an uneventful mitral valve replacement. After cardiopulmonary bypass was terminated, brisk bleeding started from high in the posterior left ventricular wall, typical of a type III defect. We undertook external repair, placing a plug of Teflon felt into the cavity of the rupture and sandwiching it into place with pledgeted mattress and figure-of-8 sutures. The space occupied by the plug decreased the distance needed to obliterate the defect and thereby reduced the tension on the sutures necessary to achieve hemostasis. This simple technique enabled closure of the defect and avoided collateral tears that would have compromised an otherwise successful repair. Two years postoperatively, the patient had normal mitral valve function and no left ventricular aneurysm. In addition to reporting the patient's case, we review the types of left ventricular rupture that can occur during mitral valve replacement and discuss the various repair options.

Left ventricular apical aneurysm following primary percutaneous coronary intervention.

Left ventricular apical aneurysm (LVAA) is a serious complication of acute anterior myocardial infarction (MI). The purpose of our study was to investigate the clinical features of LVAA in the primary PCI era. A total of 161 acute anterior MI patients who had primary PCI and had an echocardiogram on chronic phase were included. The development of LVAA was reviewed on chronic phase. Univariate and multivariate logistic regression analyses were performed to identify the predictors of LVAA. Primary stenting was performed in 160 patients (99.4 %). Procedural success was obtained in all patients with a final TIMI flow grade 3 obtained in 142 patients (88.2 %). LVAA developed in the chronic phase in 29 patients (18.0 %). Multivariate logistic regression analysis revealed that peak CK (500 mU/ml increase; OR 1.24, 95 % CI 1.09-1.41, p = 0.001), heart rate at discharge (5/min increase; OR 1.39, 95 % CI 1.03-1.87, p = 0.03), final TIMI flow grade ≤2 (vs. TIMI 3; OR 6.95, 95 % CI 1.70-28.36, p = 0.01) and final myocardial brush grade (MBG) ≤2 (vs. MBG 3; OR 4.33, 95 % CI 1.06-17.66, p = 0.04) were significantly associated with the development of LVAA. The initial TIMI flow grade or the grade of collateral flow was not associated with LVAA. In conclusion, peak CK, heart rate, and final TIMI flow grade or final MBG ≤2 were significantly associated with the development of LVAA. Achieving a TIMI flow grade 3 by primary PCI may be important for preventing LVAA.

Recurrent apical ballooning despite treatment with verapamil.

OBJECTIVE: To report a case of recurrent tako-tsubo syndrome that developed despite treatment with calcium channel antagonists. CASE SUMMARY: A 76-year-old woman with past medical history of ischemic heart disease and mild chronic asthma presented in 2001 with clinical characteristics and laboratory markers consistent with myocardial ischemia. Coronary angiogram was done with successful balloon angioplasty to LAD stenosis. Ventriculogram and echocardiography demonstrated apical ballooning believed to represent aneurysm formation. Several months later, a follow-up echocardiogram (ECG) revealed normal LV size and function with no wall motion abnormalities. ECG was unremarkable. In 2004, the patient was admitted with dyspnea, chest pain and ST elevation in ECG with normal troponin. Coronary angiogram demonstrated patent coronary tree. Left ventriculogram revealed apical ballooning sparing the base of the heart. Medically controlling the asthma attack led to clinical, echocardiographic and remarkable electrocardiographic normalization within days. Rest thallium perfusion scan done within 48 h demonstrated isolated fully reversible defect in the apex after 24 h suggesting a microvessel etiology. CONCLUSION: Tako-tsubo cardiomyopathy is an increasingly recognized condition. We report here the first case of tako-tsubo recurrence despite treatment with verapamil, and suggest a microvessel pathophysiology supported by rest thallium scan.

[Prevention of left ventricular aneurysm formation and left ventricular remodeling caused by percutaneous transluminal coronary angioplasty performed 24-48 hours after onset of acute myocardial infarction].

The prevention of left ventricular aneurysm formation and left ventricular remodeling by percutaneous transluminal coronary angioplasty (PTCA) performed 24 to 48 hours after onset of acute myocardial infarction was investigated. Left ventriculography and coronary angiography were performed in 25 patients within 24 hours of onset of acute myocardial infarction. The patients were divided into two groups; reperfusion group (n = 17) and successful PTCA group (n = 8). The reperfusion group and the PTCA group included patients whose infarct-related coronary arteries were successfully reperfused to 99%, Thrombolysis in Myocardial Infarction (TIMI) grade II or III, immediately after coronary thrombolysis. However, the reperfusion group did not include the patients with spontaneous reperfusion or reperfusion after PTCA. The PTCA group consisted of patients who underwent successful PTCA performed within 24 to 48 hours after onset of infarction (mean 28.4 +/- 6.0 hours). Non-reperfusion in the acute phase was defined as TIMI grade 0-I. The size of the ventricular aneurysm in the PTCA group was significantly reduced compared with the reperfusion group (PTCA group 4.2 +/- 8.7%, reperfusion group 27.2 +/- 6.6%; p < 0.01). The increase of left ventricular end-diastolic volume (delta LVEDVI) from the acute to chronic phases was calculated to estimate left ventricular remodeling. There was a significant difference between the two groups in delta LVEDVI (PTCA group 4 +/- 19 ml/m2, reperfusion group 19 +/- 17 ml/m2; p < 0.05). PTCA performed within 24 to 48 hours after onset in patients with acute myocardial infarction and infarct-related coronary arteries, resulting in reperfusion to 99% TIMI grade II or III immediately after coronary thrombolysis, prevents left ventricular aneurysm formation and remodeling.

[Correlation between the persistence of ST elevation and left ventricular aneurysm in the post-infarction period]. / Corrélation entre la persistance du sus-décalage du segment ST et l'anévrysme du ventricule gauche dans le post-infarctus.

The objective of this study was to verify whether the persistence of ST elevation on ECG after myocardial infarction was well correlated with the presence of left ventricular aneurysm. This study concerns 30 male patients with a mean age of 46 +/- 7.6 years, with ST elevation of more than 1 mm on ECG, at least 15 days after the presumed onset of myocardial infarction. All patients were investigated by echocardiography and cardiac catheterization. ST elevation was recorded in the ECG leads corresponding to the site of necrosis. 2D echocardiography identified 21 cases (70%) of left ventricular aneurysm and cardiac catheterization revealed 26 cases (86%). The electrical site of ST elevation was correlated with the site of the aneurysm. In conclusion, the persistence of ST elevation on the ECG more than 15 days after the onset of myocardial infarction has a good predictive value for the presence of left ventricular aneurysm, which can only be confirmed by cardiac catheterization.

Impact of left ventricular unloading after late reperfusion of canine anterior myocardial infarction on remodeling and function using isosorbide-5-mononitrate.

BACKGROUND: Late reperfusion during acute myocardial infarction results in delayed recovery of ventricular function and less remodeling, whereas ventricular unloading with nitrates improves function and attenuates remodeling. Whether late reperfusion combined with prolonged unloading with isosorbide-5-mononitrate (ISMN) might produce greater functional recovery and less remodeling than late reperfusion alone is not known. METHODS AND RESULTS: In vivo left ventricular function and topography (echocardiograms), postmortem topography (planimetry), and collagen (hydroxyproline) were measured in dogs that were randomized to reperfusion 2 hours after left anterior descending coronary artery ligation, and ISMN (n = 12) or placebo (n = 12) was given as 25 mg IV over 4 hours followed by 50 mg PO QID for 6 weeks. Compared with placebo, the ISMN group had similar heart rate but lower left atrial pressure, mean arterial pressure, and rate-pressure products. Although in vivo baseline remodeling and functional parameters were similar in the two groups, by 6 weeks the ISMN group had smaller (P < or = .05) infarct and noninfarct segment lengths, ventricular volumes, and mass; less (P < .001) asynergy; and greater (P < .001) ejection fraction. More important, by 2 days, ejection fraction was 18% greater (P < .025) and asynergy 26% less (P < .05) with ISMN. At 6 weeks, ISMN showed less (P < or = .05) scar size, scar collagen, cavity dilation, noninfarct wall thickness, and apical bulging than placebo. In another 4 dogs, acute ISMN produced less improvement in function and remodeling than prolonged ISMN. CONCLUSIONS: Late reperfusion of acute anterior myocardial infarction combined with prolonged ISMN unloading results in greater and earlier recovery of ventricular function and less remodeling than late reperfusion alone.

[Long term echocardiographic evaluation of thrombolytic therapy effect on regional function of and aneurysm formation in, the left ventricle in myocardial infarction]. / Odlegla ocena echokardiograficzna wplywu leczenia trombolitycznego na funkcje regionalna i powstawanie tetniaka lewej komory w zawale serca.

The late effects of thrombolytic therapy on regional left ventricular function and ventricular aneurysm formation were evaluated in 91 patients with acute myocardial infarction by two-dimensional echocardiography performed at 12 weeks and after one year follow-up. 53 patients were randomized to streptokinase plus heparin and 38 patients to heparin therapy alone. Wall motion score index (WMSI), asynergic area (AA) and left ventricular aneurysm were assessed in serial echocardiographic examination. During examination at 12 weeks of acute myocardial infarction significant differences between both groups of patients showed: WMSI 1.43 +/- 0.42 vs 1.78 +/- 0.61 (p < 0.005), AA 26.3 +/- 20.4 vs 39.4 +/- 22.8 (p < 0.01), left ventricular aneurysm 3(5.7%) vs 10(26.3%) (p < 0.05). After one year of examination significant differences persisted: WMSI 1.35 +/- 0.42 vs 1.62 +/- 0.59 (p < 0.05) AA 23.2 +/- 22.2 vs 35.8 +/- 24.8 (p < 0.02), left ventricular aneurysm 3(6.1%) vs 9(25.7%) (p < 0.05). Our data indicate that thrombolytic therapy improves late regional left ventricular function in patients with acute myocardial infarction by reducing the extent of regional wall motion abnormalities. We find evident reduction in aneurysm formation due to acute myocardial infarction in survivors after 12 weeks of observation. The mentioned beneficial effects are noted at least up to one year after acute myocardial infarction.

Bivalent effects of human growth hormone in experimental myocardial infarcts. Protective when administered alone and aggravating when combined with beta blockers.

Human growth hormone (hGH) administered alone revealed itself as a useful drug to prevent ventricular aneurysm formation in experimental myocardial infarctions in rats and is also able to diminish and change the usually expected pattern of wall necrosis. A protective action on the collagen framework of myocytes has been confirmed as one of the main causes responsible for the above mentioned findings. There are other positive metabolic actions on the myocardial cell although not completely known yet. These actions are revealed by an atypical picture of infarction which appears regionally reduced and with a patchy intracellular distribution. In an opposite fashion, when hGH was administered together with beta blockers, a rapid and extensive deleterious action occurred at the ventricular wall, a very high incidence of ventricular aneurysms and an increased extension of myocardial infarcts were the most outstanding features. The histologic picture in this series resembles that of a rapidly evolving diabetic cardiomyopathy.

[Post-infarct myocardial remodelling: from experimental data to the prevention of heart failure]. / Remodelamiento miocárdico post infarto del miocardio: desde los datos experimentales a la prevención de insuficiencia cardiaca.

Structural and biochemical modifications of the myocardium (remodeling) occur after acute myocardial infarction. An important part of this process of myocardial remodeling takes place in the interstitial compartment which is composed mainly of fibrillar collagen. These remodeling changes are associated with modifications in left ventricular geometry and function that could be deleterious and have significant clinical manifestations. Some salutary effects of the treatment are related to modifications of the process of interstitial remodeling. Clinical studies with calcium channel antagonists, nitrates and, specially converting enzyme inhibitors have shown significant improvement in the degree of ventricular dilation, hemodynamics and exercise tolerance as a compared to placebo treated patients. Ongoing clinical studies will provide us with more definite information on the effects of converting enzyme inhibitors on long term prognosis as well as on myocardial remodeling after acute myocardial infarction.

Importance of collateral circulation for prevention of left ventricular aneurysm formation in acute myocardial infarction.

The effect of preexistent coronary collateral perfusion on the prevention of left ventricular aneurysm formation was examined in 47 patients undergoing an intracoronary thrombolysis within 6 hours after the onset of a first acute anterior myocardial infarction. Left ventricular aneurysm formation and wall motion were analyzed with cineventriculography. A left ventricular aneurysm was determined as well-defined demarcation of the infarcted segment from normally contracting myocardium. In 25 patients with successful thrombolysis (group A), a left ventricular aneurysm was observed in one patient (4%) during the chronic stage of infarction. In 10 patients who had a significant collateral circulation to the infarct-related coronary artery and unsuccessful reperfusion (group B), the left ventricular aneurysm was observed in only one patient (10%). In the remaining 12 patients with unsuccessful recanalization in the absence of a significant collateral perfusion (group C), there was a higher incidence (seven of 12, 58%) of left ventricular aneurysm formation than in groups A and B (p less than 0.05). In group A, both the global ejection fraction and regional wall motion in the infarct areas improved significantly (p less than 0.05) between the acute and chronic stages of infarction. By contrast, in groups B and C, these indexes on the ventricular function did not change significantly during the convalescent period. Thus, although the collateral perfusion existing at the onset of acute myocardial infarction may not improve ventricular function, it exerts a beneficial effect on the prevention of left ventricular aneurysm formation.

Limitation of myocardial infarct expansion by reperfusion independent of myocardial salvage.

Very early reperfusion after coronary occlusion can reduce infarct size and preserve left ventricular function. Whether later reperfusion is of benefit is unclear. We studied the effect of very early reperfusion with myocardial salvage and "late" reperfusion without myocardial salvage on infarct expansion and aneurysm formation. Sixty-eight rats underwent left coronary artery ligation and were randomized to 30 min reperfusion, 2 hr reperfusion, or permanent coronary artery ligation. The animals were killed and the hearts examined at 2 weeks. Thirty minute reperfusion reduced infarct size, extent of transmurality, and infarct expansion. Two hour reperfusion reduced neither infarct size nor transmurality but inhibited infarct expansion. The results of this study in the rat preparation suggest a beneficial effect of "late" reperfusion on infarct expansion independent of myocardial salvage. If these results are confirmed in human beings, the period after myocardial infarction during which a patient can be considered for thrombolytic therapy or reperfusion by percutaneous transluminal coronary angioplasty could be greatly prolonged.

Late effects of intracoronary streptokinase on regional wall motion, ventricular aneurysm and left ventricular thrombus in myocardial infarction: results from the Western Washington Randomized Trial.

To determine whether intracoronary streptokinase improves late regional wall motion or reduces left ventricular aneurysm or thrombus formation in patients with acute myocardial infarction, two-dimensional echocardiography was performed at 8 +/- 3 weeks after infarction in 83 patients randomized to streptokinase (n = 45) or standard therapy (n = 38) in the Western Washington Intracoronary Streptokinase Trial. Among the patients treated with streptokinase, the average time to treatment was 4.7 +/- 2.5 hours after the onset of chest pain, and 67% had successful reperfusion. Regional wall motion was assessed in nine left ventricular segments on a scale of 1 to 4 (normal, hypokinetic, akinetic and dyskinetic). Left ventricular thrombus formation was interpreted as positive, equivocal or negative. All patients received anticoagulant therapy in the hospital and 52 received such therapy after hospital discharge. The mean (+/- SD) global (1.5 +/- 0.4 in both groups) and regional wall motion scores in the streptokinase-treated and control groups were not significantly different. The prevalence of aneurysm was 16% in both groups. Left ventricular thrombus was identified in only five patients (positive identification in four, and equivocal in one), all in the streptokinase-treated group (p = NS). There were also no differences between streptokinase and control treatment in any of the echocardiographic variables in subgroups of patients with anterior infarction, inferior infarction, no prior infarction or reperfusion with streptokinase. It is concluded that intracoronary streptokinase given relatively late in the course of acute myocardial infarction does not result in improved global or regional wall motion or a reduction in left ventricular thrombus or aneurysm formation in survivors studied 2 months after myocardial infarction.