Wissam Jaber

Diastolic relaxation and compliance reserve during dynamic exercise in heart failure with preserved ejection fraction

Background Recent studies have examined haemodynamic changes with stressors such as isometric handgrip and rapid atrial pacing in heart failure with preserved ejection fraction (HFpEF), but little is known regarding left ventricular (LV) pressure–volume responses during dynamic exercise. Objective To assess LV haemodynamic responses to dynamic exercise in patients with HFpEF. Methods Twenty subjects with normal ejection fraction (EF) and exertional dyspnoea underwent invasive haemodynamic assessment during dynamic exercise to evaluate suspected HFpEF. Results LV end-diastolic pressure was elevated at rest (>15 mm Hg, n=18) and with exercise (≥20 mm Hg, n=20) in all subjects, consistent with HFpEF. Heart rate (HR), blood pressure, arterial elastance and cardiac output increased with exercise (all p<0.001). Minimal and mean LV diastolic pressures increased by 43–56% with exercise (both p<0.0001), despite a trend towards a reduction in LV end-diastolic volume (p=0.08). Diastolic filling time was abbreviated with increases in HR and the proportion of diastole that elapsed prior to estimated complete relaxation increased (p<0.0001), suggesting inadequate relaxation reserve relative to the shortening of diastole. LV diastolic chamber elastance acutely increased 50% during exercise (p=0.0003). Exercise increases in LV filling pressures correlated with changes in diastolic relaxation rates, chamber stiffness and arterial afterload but were not related to alterations in preload volume, HR or cardiac output. Conclusion In patients with newly diagnosed HFpEF, LV filling pressures increase during dynamic exercise in association with inadequate enhancement of relaxation and acute increases in LV chamber stiffness. Therapies that enhance diastolic reserve function may improve symptoms of exertional intolerance in patients with hypertensive heart disease and early HFpEF.

Acute Pulmonary Embolism: With an Emphasis on an Interventional Approach.

Compared with recent advances in treatment of serious cardiovascular diseases, such as myocardial infarction and stroke, the treatment and outcome of acute pulmonary embolism (PE) have remained relatively unchanged over the last few decades. This has prompted several experts to call for the formation of multidisciplinary PE response teams with a more proactive approach to the treatment of PE. In the current document, we discuss the formation of such teams and describe the available treatment options beyond anticoagulation, with a focus on the interventional approach. Acknowledging the paucity of data to support widespread adoption of such techniques, we call for the collection of outcomes data in multicenter registries and support for randomized trials to evaluate interventional treatments in patients with high-risk PE.

Differentiation of tricuspid regurgitation from constrictive pericarditis: novel criteria for diagnosis in the cardiac catheterisation laboratory

Background: Severe tricuspid regurgitation, constrictive pericarditis and restrictive cardiomyopathy can all present with signs and symptoms of right heart failure and similar haemodynamic findings of elevation and equalisation of diastolic pressures at catheterisation. Although catheterisation findings of enhancement of ventricular interaction are a reliable parameter to distinguish constrictive pericarditis from restrictive cardiomyopathy, this also may be present in severe tricuspid regurgitation. Objective: To identify unique haemodynamic parameters that differentiate severe tricuspid regurgitation from constrictive pericarditis. Methods: Haemodynamic findings from simultaneous right and left heart catheterisation of 14 patients (age 59 years; men 71%) with documented severe tricuspid regurgitation (group I) were compared with those of 14 patients with surgically proven constrictive pericarditis (group II). Results: Findings of elevated right atrial pressure, early rapid ventricular filling and expiratory equalisation of ventricular diastolic pressures were similar in both groups. Ventricular interdependence, assessed by interaction of left ventricular (LV) and right ventricular (RV) systolic pressures, was also present in both groups. Relative changes in LV and RV diastolic pressures during respiration reliably distinguished group I from group II. During inspiration, the difference between the LV and RV diastolic pressures widened in group I but narrowed in group II. The height and slope of the early rapid filling wave in RV pressure trace was accentuated during inspiration in group I but did not change in group II. Conclusions: The haemodynamic findings at cardiac catheterisation in patients with severe, symptomatic tricuspid regurgitation are similar to those of constrictive pericarditis. Careful analysis of the relationship of the LV and RV diastolic pressures during respiration can help differentiate the two entities.

Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated Cardiomyopathy Functional Implications and Mechanistic Insight

Background—Altered titin isoforms may modify cardiac function in heart failure (HF), but the nature of isoform switches and associated functional implications are not well defined. Limited studies have reported an increased compliant isoform (N2BA) expression in human systolic HF. Titin may also modulate stretch-regulated responses such as myocardial natriuretic peptide production. Methods and Results—We characterized titin isoform expression and extracellular matrix in all 4 cardiac chambers and the left ventricular (LV) epicardium and endocardium in normal dogs (n=6) and those with HF (n=6) due to tachypacing and characterized functional implications at the LV myofiber and chamber level. Recognizing the potential for uncoupling of the extracellular matrix and cardiomyocyte in tachypacing, myocardial natriuretic peptide production, a molecular marker of stretch-regulated responses, was also assessed. All chambers were dilated in HF, but the extracellular matrix was not increased. HF dogs had markedly lower N2BA in the atria and right ventricle. In failing LVs, N2BA was decreased only in the epicardium, where myofiber passive stiffness was increased. However, LV chamber mechanics were driven by the marked LV dilatation, with no increase in LV diastolic stiffness. Natriuretic peptide concentrations increased markedly in the endocardium in relation to increases in LV wall stress. Conclusions—Tachypacing HF is characterized by decreases in compliant titin isoform expression in the atria, right ventricle, and LV epicardium. However, LV chamber mechanics are principally determined by geometric and extracellular matrix changes rather than titin-based myofiber stiffness in this model. Stretch-regulated myocardial responses (natriuretic peptide production) appeared intact, suggesting that the mechanotransduction role of titin was not impaired in HF.

Safety of catheter‐directed thrombolysis for massive and submassive pulmonary embolism: Results of a multicenter registry and meta‐analysis

To evaluate the safety and efficacy of catheter‐directed thrombolysis (CDT) in the treatment of acute pulmonary embolism (PE).

Titin Isoforms, Extracellular Matrix, and Global Chamber Remodeling in Experimental Dilated CardiomyopathyCLINICAL PERSPECTIVE

Background—Altered titin isoforms may modify cardiac function in heart failure (HF), but the nature of isoform switches and associated functional implications are not well defined. Limited studies have reported an increased compliant isoform (N2BA) expression in human systolic HF. Titin may also modulate stretch-regulated responses such as myocardial natriuretic peptide production. Methods and Results—We characterized titin isoform expression and extracellular matrix in all 4 cardiac chambers and the left ventricular (LV) epicardium and endocardium in normal dogs (n=6) and those with HF (n=6) due to tachypacing and characterized functional implications at the LV myofiber and chamber level. Recognizing the potential for uncoupling of the extracellular matrix and cardiomyocyte in tachypacing, myocardial natriuretic peptide production, a molecular marker of stretch-regulated responses, was also assessed. All chambers were dilated in HF, but the extracellular matrix was not increased. HF dogs had markedly lower N2BA in the atria and right ventricle. In failing LVs, N2BA was decreased only in the epicardium, where myofiber passive stiffness was increased. However, LV chamber mechanics were driven by the marked LV dilatation, with no increase in LV diastolic stiffness. Natriuretic peptide concentrations increased markedly in the endocardium in relation to increases in LV wall stress. Conclusions—Tachypacing HF is characterized by decreases in compliant titin isoform expression in the atria, right ventricle, and LV epicardium. However, LV chamber mechanics are principally determined by geometric and extracellular matrix changes rather than titin-based myofiber stiffness in this model. Stretch-regulated myocardial responses (natriuretic peptide production) appeared intact, suggesting that the mechanotransduction role of titin was not impaired in HF.

Immediate improvement in coronary flow reserve after alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy

Objectives: To examine whether percutaneous alcohol septal ablation affects coronary flow reserve (CFR) in patients with hypertrophic cardiomyopathy (HCM). Methods: CFR was measured immediately before and after septal ablation in patients with symptomatic obstructive HCM. CFR was also obtained in normal subjects (NL) for comparison. Results: Patients with HCM (n = 11), compared with NL (n = 22), had a lower mean (SD) baseline CFR (1.96 (0.5) vs 3.0 (0.7), p<0.001), a lower coronary resistance (1.04 (0.45) vs 3.0 (2.6), p = 0.002), a higher coronary diastolic/systolic velocity ratio (DSVR; 5.1 (3.0) vs 1.8 (0.5), p = 0.04) and a lower hyperaemic coronary flow per left ventricular (LV) mass (0.73 (0.4) vs 1.1 (0.6) ml/min/g, p = 0.007). Septal ablation in the HCM group (n = 7) reduced the outflow tract gradient but not the left atrial or LV diastolic pressures. Ablation resulted in immediate normalisation of CFR (to 3.1 (1), p = 0.01) and DSVR (to 1.9 (0.8), p = 0.09) and an increase in coronary resistance (to 1.91 (0.6), p = 0.02). This was probably related to an improvement in the systolic coronary flow. Conclusions: This study demonstrates that successful septal ablation in patients with symptomatic HCM results in immediate improvement in CFR, which is reduced in HCM partly because of the increased systolic contraction load.

Malignant tracheal-mediastinal-parenchymal-pleural fistula after chemoradiation plus bevacizumab: management with a Y-silicone stent inside a metallic covered stent.

Tracheal or bronchial-mediastinal fistulas are a rare entity associated to high mortality. We report a case of a 58-year-old man with an unresectable non-small cell carcinoma of the lung, treated with chemoradiation followed by bevacizumab. Approximately, 6 weeks after starting bevacizumab he developed a severe cough with copious secretions He could not lie supine due to the feeling of drowning. Investigations revealed a large tracheo-mediastinal-parenchymal-pleural fistula. Palliative management was offered with interventional bronchoscopic techniques. He was found to have a large central airway defect that obliterated almost 40% of the trachea. Under general anesthesia and positive pressure ventilation, a unique approach was used to rebuild an eroded tracheal and right main stem bronchial wall. A self-expanding metallic stent (SEMS) was placed to provide a scaffold of support, whereas a Dumon Y-stent was placed inside the SEMS. This combination allowed for a patent, stable airway; recreating the normal anatomy in a minimally invasive manner walling off the fistula. The patient was discharged 2 days after the bronchoscopic intervention, with significant palliation of his symptomatology. Eighteen months later, the upper lobe cavity persists with a stable airway and stents perfectly positioned with clinically insignificant evidence of stent related granulation in the upper trachea.

The impact of clopidogrel therapy on postoperative bleeding after robotic-assisted coronary artery bypass surgery.

OBJECTIVES The purpose of this study was to determine whether patients undergoing robotic-assisted coronary artery bypass graft surgery (CABG) on clopidogrel had an increased risk of bleeding complications compared with those not on clopidogrel. METHODS From 2008 to 2011, 322 patients underwent robotic-assisted CABG either as an isolated procedure or as part of a hybrid coronary revascularization procedure (HCR). Patients were classified according to whether they received clopidogrel within 5 days of surgery or intraoperatively (n = 64) compared with those who never received or who had discontinued clopidogrel therapy >5 days before surgery (n = 258). A propensity analysis using 31 preoperative variables was used to control for confounding variables. In a subgroup analysis, patients undergoing one-stage HCR (clopidogrel load 600 mg in odds ratio (OR) prior to stenting) were compared with patients in the clopidogrel group who underwent two-stage HCR. RESULTS In the Clopidogrel group, the mean interval between surgery and last dose of clopidogrel was 2.1 ± 1.5 days. Compared with the No Clopidogrel group, the Clopidogrel group had greater 24-h chest tube drainage (1003 ± 572 vs 782 ± 530 ml, P = 0.004) and more blood transfusions (35.9%, 23 of 64 patients vs 20.9%, 54 of 258 patients, P = 0.01). On logistic regression analysis, there was greater 24-h chest tube drainage in the Clopidogrel group (+198 ml, P = 0.02) and a significantly higher incidence of blood transfusion (OR = 2.30, P = 0.01). In the subgroup analysis, patients undergoing one-stage HCR (n = 17) had greater 24-h chest tube drainage compared with patients undergoing two-stage HCR (1262 vs 909 ml, P = 0.03). CONCLUSIONS Patients undergoing robotic-assisted CABG on clopidogrel had more postoperative bleeding and a higher incidence of blood transfusion. Therefore, despite a less invasive approach, surgery should be delayed in these patients when possible.

Carcinoid Heart Disease

A 57-year-old man presented with peripheral edema, fatigue, and dyspnea on exertion. He also had diarrhea and occasional flushing for 4 months. On physical examination he had elevated neck veins at 9 cm with a dominant v-wave, sternal lift with 2/6 systolic ejection murmur at the left upper sternal border and holosystolic murmur at the left lower sternal border, and a moderate lower extremity edema. His echocardiogram is shown (Figure 1). In a 24-hour urine collection, 5-hydroxyindolacetic …