Ricardo Krakover

The role of cardiac power and systemic vascular resistance in the pathophysiology and diagnosis of patients with acute congestive heart failure.

Conventional hemodynamic indexes (cardiac index (CI), and pulmonary capillary wedge pressure) are of limited value in the diagnosis and treatment of patients with acute congestive heart failure (CHF).

Acute heart failure: a novel approach to its pathogenesis and treatment.

Acute heart failure (HF) is one of the most common syndromes in emergency medicine, however, its exact pathogenesis has remained largely unknown. Based on clinical and hemodynamic data we have sub‐divided acute HF into four syndromes: cardiogenic shock, pulmonary edema, hypertensive crisis and exacerbated HF. Cardiogenic shock is caused by a severe reduction in cardiac power which is not met by an adequate increase in peripheral vascular resistance leading to significant decrease in blood pressure and end organ perfusion. Hence the treatment of cardiogenic shock should be directed at improving cardiac performance (by optimizing filling pressure, intra‐aortic balloon pump and immediate revascularization) and administration of peripheral vasoconstrictors. The other acute HF syndromes (pulmonary edema, HTN crisis and exacerbated HF) are caused by a combination of progressive excessive vasoconstriction superimposed on reduced left ventricular functional reserve. The impaired cardiac power and extreme vasoconstriction induce a vicious cycle of afterload mismatch resulting in a dramatic reduction of CO and elevated left ventricular end diastolic pressure, which is transferred backwards to the pulmonary capillaries yielding pulmonary edema. Therefore, the immediate treatment of these acute HF syndromes should be based on the administration of strong, fast‐acting intravenous vasodilators such as nitrates or nitroprusside. After initial stabilization, therapy should be directed at reducing recurrent episodes of acute HF, by prevention of repeated episodes of excessive vasoconstriction along with efforts to optimize cardiac function.

Circumferential and Longitudinal Strain in 3 Myocardial Layers in Normal Subjects and in Patients with Regional Left Ventricular Dysfunction

BACKGROUND The left ventricle is not homogenous and is composed of 3 myocardial layers. Until recently, magnetic resonance imaging has been the only noninvasive technique for detailed evaluation of the left ventricular (LV) wall. The aim of this study was to analyze strain in 3 myocardial layers using speckle-tracking echocardiography. METHODS Twenty normal subjects and 21 patients with LV dysfunction underwent echocardiography. Short-axis (for circumferential) and apical (for longitudinal strain) views were analyzed using modified speckle-tracking software enabling the analysis of strain in 3 myocardial layers. RESULTS In normal subjects, longitudinal and circumferential strain was highest in the endocardium and lowest in the epicardium. Longitudinal endocardial and mid layer strain was highest in the apex and lowest in the base. Epicardial longitudinal strain was homogenous over the left ventricle. Circumferential 3-layer strain was highest in the apex and lowest in the base. In patients with LV dysfunction, strain was lower, with late diastolic or double peak. CONCLUSIONS Three-layer analysis of circumferential and longitudinal strain using speckle-tracking imaging can be performed on a clinical basis and may become an important method for the assessment of real-time, quantitative global and regional LV function.

Clinical and hemodynamic effects of bosentan dose optimization in symptomatic heart failure patients with severe systolic dysfunction, associated with secondary pulmonary hypertension--a multi-center randomized study.

Objective: Toevaluate the effects of bosentan on echo-derived hemodynamic measurements, and clinical variables in symptomatic heart failure (HF) patients. Method: Multi- center, double-blind, randomized (2:1), placebo-controlled study comparing bosentan (8–125 mg b.i.d.) to placebo in patients with New York Heart Association class IIIb–IV HF, left ventricular ejection fraction <35% and systolic pulmonary artery pressure (SPAP) >40 mm Hg. Primary and secondary endpoints were change from baseline to 20 weeks in SPAP and cardiac index, respectively. Safety endpoints were treatment emergent adverse events (AEs), change in body weight, hemoglobin, hematocrit, systolic blood pressure and diuretic use. Results: Ninety-four patients enrolled: 60 to bosentan, 34 to placebo. There was no significant difference between the 2 arms in SPAP change (0.1 ± 11.5 mm Hg , 95% confidence limit (CL) –5.4 to 5.2, p = 0.97), cardiac index shift (0.12 ± 0.45, 95% CL –0.09 to 0.33 , p = 0.24 ) or any of the other 22 echocardigraphic measurements obtained. Therapy-duration was longer in the placebo arm, while more patients in the bosentan arm experienced adverse and serious AEs. Conclusion: In HF patients with left ventricular dysfunction and secondary pulmonary hypertension, bosentan did not provide any measurable hemodynamic benefit, and was associated with more frequent AEs, requiring drug discontinuation.

Minimal heparinization in coronary angioplasty—how much heparin is really warranted?

The purpose of the study was to assess the results of percutaneous transluminal coronary angioplasty (PTCA), performed with a single intravenous bolus of 2,500 U of heparin, in a nonemergency PTCA cohort. Three hundred of 341 consecutive patients (87.9%) undergoing PTCA were prospectively enrolled in the study. They received heparin, 2,500-U intravenous bolus, before PTCA, with intention of no additional heparin administration. Patient and lesion characteristics as well as PTCA results were evaluated independently by 2 physicians. Patients were followed up by structured telephone questionnaires at 1 and 6 months after PTCA. Mean activated clotting time obtained 5 minutes after heparin administration was 185+/-19 seconds (range 157 to 238). There were 3 (1%) in-hospital major adverse cardiovascular events: 2 deaths (0.66%), 1 (0.33%) Q-wave myocardial infarction. Emergency coronary surgery and stroke were not reported. Six patients (2%) experienced abrupt coronary occlusion within 14 days after PTCA, warranting repeat target vessel revascularization. Angiographic and clinical success were achieved in 96% and 93.3%, respectively. No bleeding or vascular complications were recorded. Six-month follow-up (184 patients) revealed 3 cardiac deaths (1 arrhythmic, 2 after cardiac surgery), 1 Q-wave myocardial infarction, and 9.7% repeat target vessel revascularization. This study suggests that very low doses of heparin and reduced activated clotting time target values are safe in non-emergency PTCA, and can reduce bleeding complications, hospital stay, and costs. Larger, randomized, double-blind heparin dose optimization studies need to confirm this notion.

Pulmonary edema: new insight on pathogenesis and treatment.

Pulmonary edema is one of the most serious and life-threatening situations in emergency medicine. Lately it has become apparent that in most cases pulmonary edema is not caused by fluid accumulation but rather fluid redistribution that is directed into the lungs because of heart failure. Based on a series of recently published studies, we propose that often the pathogenesis of pulmonary edema is related to a combination of marked increase in systemic vascular resistance superimposed on insufficient systolic and diastolic myocardial functional reserve. This resistance results in increased left ventricular diastolic pressure causing increased pulmonary venous pressure, which yields a fluid shift from the intravascular compartment into the pulmonary interstitium and alveoli, inducing the syndrome of pulmonary edema. Therefore, the emphasis in treating pulmonary edema has shifted from diuretics (ie, furosemide) to vasodilators (ie, high-dose nitrates) combined with noninvasive positive airway pressure ventilation and rarely inotropes. New classes of drugs that are currently being investigated for treating decompensated heart failure such as natriuretic peptides, calcium promoters, and endothelin antagonist are also being assessed for treating pulmonary edema. This review will explore this new hypothesis put forward to explain the pathogenesis of pulmonary edema and the evolving management strategies.

Early Thrombolytic Therapy Does Not Enhance the Recovery of the Right Ventricle in Patients with Acute Inferior Myocardial Infarction and Predominant Right Ventricular Involvement

In this study we report the effects of early thrombolytic therapy on the recovery of the right ventricle after an acute myocardial infarction. Sixty-five patients presenting with their first inferior myocardial infarction and predominant right ventricular involvement were consecutively treated as follows: group A (20 patients) conservatively (without thrombolytic therapy), group B (19 patients) with streptokinase and group C (26 patients) with recombinant tissue type plasminogen activator. Coronary angiography was performed within 72 h after admission in 52 patients (10 of group A, 18 of group B and in 24 patients of group C) followed by transluminal coronary angioplasty in 26. All groups had similar characteristics except for a higher mean age in group A. Within 3 months, a remarkable improvement in right ventricular function and a major increase in ejection fraction was observed for all three patient groups. Improvement of right ventricular function was more prominent in patients with residual flow through the infarct-related artery. The beneficial course was comparable in all the groups, unaffected by the type of medical treatment applied, or by the performance of coronary angioplasty. No further significant change occurred beyond this period. Thus, early thrombolytic therapy does not augment the generally favorable course of recovery of the right ventricle from acute infarction.

Long-Term (>3 Years) Outcome and Predictors of Clinical Events After Insertion of Sirolimus-Eluting Stent in One or More Native Coronary Arteries (from the Israeli Arm of the e-Cypher Registry)

The aim of this study was to evaluate long-term (3.4 years) outcomes and predictors of clinical events in patients treated with sirolimus-eluting stents in the Israeli arm of the e-Cypher registry. From July 2002 to October 2003, 488 patients from 8 medical centers in Israel were enrolled in the e-Cypher registry. Nineteen patients with interventions in venous grafts were excluded from the final analysis. Long-term follow-up was completed for 98% of the remaining patients. There were 29 cases (6.3%) of death (3.9% cardiac and 2.4% noncardiac deaths). According to the broad academic research consortium definition of stent thrombosis, there were 19 cases (4%) of stent thrombosis (incidence density 0.9 cases/100 patient-years). There were 46 cases (9.9%) of target lesion revascularization and 76 cases (16.3%) of major adverse cardiac events (combination of death, myocardial infarction, and target lesion revascularization). Independent predictors of stent thrombosis were renal failure (hazard ratio 9.6, 95% confidence interval 1.9 to 47), stent length (hazard ratio 1.1, 95% confidence interval 1 to 1.2), and the off-label use of sirolimus-eluting stents (hazard ratio 5.3, 95% confidence interval 1.2 to 24). In conclusion, during >3 years of follow-up, stent thrombosis, major adverse cardiac events, and target lesion revascularization continued at constant rates over time. Clinical parameters such as renal failure and procedural parameters such as off-label use and stent length were independent predictors of stent thrombosis.

Speckle Tracking Imaging in Acute Inflammatory Pericardial Diseases

Background: Left ventricular (LV) function in acute perimyocarditis is variable. We evaluated LV function in patients with acute perimyocarditis with speckle tracking. Methods: Thirty‐eight patients with acute perimyocarditis and 20 normal subjects underwent echocardiographic examination. Three‐layers strain and twist angle were assessed with a speckle tracking. Follow‐up echo was available in 21 patients. Results: Strain was higher in normal subjects than in patients with perimyocarditis. Twist angle was reduced in perimyocarditis—10.9°± 5.4 versus 17.6°± 5.8, P < 0.001. Longitudinal strain and twist angle were higher in normal subjects than in patients with perimyocarditis and apparently normal LV function. Follow‐up echo in 21 patients revealed improvement in longitudinal strain. Conclusions: Patients with acute perimyocarditis have lower twist angle, longitudinal and circumferential strain. Patients with perimyocarditis and normal function have lower longitudinal strain and twist angle. Short‐term follow‐up demonstrated improvement in clinical parameters and longitudinal strain despite of residual regional LV dysfunction. (Echocardiography 2011;28:548‐555)

A highly unusual right atrial mass presented in two women

Intravenous leiomyomatosis is a rare, benign neoplasm of the uterine, affecting adult women. We report two cases in whom intravenous leiomyomatosis extended through the inferior vena cava into the right heart chambers and the pulmonary artery. Both patients underwent staged operation with excision of the cardiac and primary tumour. The differential diagnosis of a right atrial mass in middle-aged women should include intravenous leiomyomatosis.