Howard R. Lee

Predictors for the development of severe tricuspid regurgitation with anatomically normal valve in patients with atrial fibrillation.

Background and Aims: Atrial fibrillation (AF) may be a risk factor for severe functional tricuspid valve regurgitation (FTR). We aimed to determine the predictors of severe FTR in patients with AF. Methods and Results: From our echocardiographic laboratory database, we searched for and reviewed the medical records of consecutive patients with severe FTR and AF seen at Mayo Clinic in Arizona from 2002 through 2009. Our search identified 42 patients who met all inclusion criteria. These patients (cases) with severe FTR and AF were compared with 38 patients (controls) with AF who had no greater than mild tricuspid regurgitation. Case patients with severe FTR were older than controls (mean, 81 years vs. 76 years; P < 0.001) and more frequently had chronic AF (69% vs 26%; P < 0.001). Mean right atrial volume (86 mL/m2 vs 46 mL/m2; P < 0.001), right ventricular volume (42 mL ± 33 mL vs 22 mL ±8 mL; P < 0.001) and tricuspid annular diameter (3.6 cm vs 3.0 cm; P < 0.001) were larger in cases than in controls. Patients with severe FTR also had a higher prevalence of right‐sided heart failure (69% vs 16%; P < 0.001). After adjusting for age and gender, right atrial and right ventricular volumes were independent predictors for the development of severe FTR in patients with AF (odds ratio, 1.7 [95% CI, 1.3–2.8] for every 10 mL/m2 increase in right atrial volume; P = 0.0002 and odds ratio, 3.1 [95% CI, 1.5–8.9] for every 10 mL increase in right ventricular volume; P = 0.0002). Conclusions: Severe FTR occurs in older patients with chronic AF as a result of marked right atrial and right ventricular dilatation; and enlargement of the tricuspid annulus in the absence of pulmonary hypertension. More importantly, severe FTR leads to increased prevalence of right‐sided heart failure underscoring the nonbenign nature of chronic AF. (Echocardiography 2012;29:140‐146)

Transient left ventricular apical ballooning syndrome (Takotsubo cardiomyopathy) following orthotopic liver transplantation

We report the first published case of transient left ventricular apical ballooning syndrome (Takotsubo cardiomyopathy) in the setting of orthotopic liver transplantation. A 65-year-old female with end-stage liver disease secondary to nonalcoholic steatohepatitis with stage 2 hepatocellular carcinoma underwent successful total hepatectomy, portal vein thrombectomy, and orthotopic liver transplantation. The patient’s past medical history included chronic systemic hypertension without prior history of cardiac disease, diabetes, smoking, hyperlipidemia, or illicit drug use. Pretransplant dobutamine stress echocardiography demonstrated hyperdynamic left ventricular function (ejection fraction 74%) with normal left ventricular size. A double product (defined as maximal systolic blood pressure heart rate) of 21,714 and heart rate of 91% of maximum predicted were achieved. There were no stress-induced wall motion abnormalities. Cardiac valves were normal. Estimated right ventricular systolic pressure was 36 mm Hg. The intraoperative course was very unremarkable. The patient had an estimated blood loss of 500 mL and received one unit of platelets. The patient did not require pressors during the procedure and had no hemodynamic instability. Thromboelastogram during the procedure did not reveal any evidence of hypercoagulation state. The posttransplantation course was uneventful until 4 hours after transplant when ST elevation was noted on the telemetry monitor. A 12-lead electrocardiogram demonstrated ST segment elevation consistent with an acute anterolateral myocardial infarction (Fig. 1A). The patient was sedated but arousable and denied chest discomfort or dyspnea. An emergent echocardiogram demonstrated anteroapical, apical, and inferoapical akinesis, consistent with an anterior myocardial infarction (Fig. 2A and B). Emergent coronary angiography demonstrated normal coronary arteries and left ventriculography confirmed the apical wall motion abnormalities. A preliminary diagnosis of transient left ventricular apical ballooning syndrome (Takotsubo cardiomyopathy) was made. Peak total creatine kinase levels were 869 U/L (normal 38–176) and troponin levels were 0.15 ng/mL (normal 0.03 ng/mL). The patient’s subsequent hospital course was unremarkable. Outpatient transthoracic echocardiogram 6 weeks later (Fig. 2C) showed normal left ventricular function with no wall motion abnormalities, and an electrocardiogram 4 months later (Fig. 1B) demonstrated normal findings with resolution of ST segment elevation. Transient left ventricular apical ballooning syndrome or Takotsubo cardiomyopathy is an uncommon cardiac abnormality that characteristically occurs in postmenopausal women following an emotional or physical stressor. The clinical presentation is similar to an acute myocardial infarction with chest pain, elevated cardiac biomarkers, and precordial ST elevation on the electrocardiogram. Coronary angiography shows nonobstructive coronary artery disease with ballooning of the apical left ventricle most commonly; however, midventricular ballooning has been reported. The pathophysiologic mechanism is not known. Leading hypotheses include catecholamine-mediated myocardial injury,

Amplatzer PFO occluder device may prevent recurrent stroke in patients with patent foramen ovale and cryptogenic stroke: a meta-analysis of randomised trials.

OBJECTIVE To review efficacy of percutaneous closure of patent foramen ovale compared with medical therapy in prevention of recurrent strokes in patients with cryptogenic stroke. METHODS AND RESULTS Electronic databases; PUBMED, EMBASE, Cochrane registry and web of knowledge were searched for relevant studies. In three randomised clinical trials involving 2303 participants, risk of the recurrent strokes (pooled HR 0.62, 95% CI=0.36-1.07, P=0.09, I(2) =10%) did not show benefit with device closure when compared with medical therapy group on meta-analysis of all three trials. However, on sensitivity analysis in trials using Amplatzer PFO occluder device, the closure of PFO was associated with significantly lower recurrent strokes (pooled HR=0.44, 95% CI=0.21-0.94, P=0.03, I(2)=0%) compared with medical therapy. CONCLUSION The closure of PFO with Amplatzer PFO occluder device was associated with significant reduction in recurrent strokes in patients with cryptogenic stroke and patent foramen ovale. The better outcome in prevention of secondary stroke in patients with cryptogenic stroke and PFO may be associated with type of closure device used.

Preventive PCI versus culprit lesion stenting during primary PCI in acute STEMI: a systematic review and meta-analysis

Aim The benefit of preventive percutaneous coronary intervention (PCI) in ST elevation myocardial infarction (STEMI) has been shown in randomised trials. However, all the randomised trials are underpowered to detect benefit in cardiac death. We aim to systematically review evidence on the cardiac mortality benefit of preventive PCI in patients presenting with acute STEMI in randomised patient populations. Methods PubMed, Scopus, Cochrane and clinicaltrials.gov databases were searched for studies published until 30 September 2013. The studies were limited to randomised clinical trials. Independent observers abstracted the data on outcomes, characteristics and qualities of studies included. Fixed effect model was employed for meta-analysis. Heterogeneity of studies included was analysed using I2 statistics. Results In three randomised clinical trials published, involving 748 patients with acute STEMI and multivessel disease, 416 patients were randomised to preventive PCI and 332 to culprit-only PCI. Patients undergoing preventive PCI had significant lower risk of cardiovascular deaths (pooled OR 0.39, 95% CI 0.18 to 0.83, p=0.01, I2=0%), repeat revascularisation (pooled OR 0.28, 95% CI 0.18 to 0.44, p=0.00001, I2=0%) and non-fatal myocardial infarction (pooled OR 0.38, 95% CI 0.20 to 0.75, p=0.005, I2=0%) compared with culprit-only revascularisation. Conclusions In patients presenting with acute STEMI and significant multivessel coronary artery disease, based on our data, preventive PCI is associated with lower risk of cardiovascular mortality compared with primary PCI of only the culprit artery. This finding needs to be confirmed in larger adequately powered randomised clinical trials.

Cardio-oncology Part I: chemotherapy and cardiovascular toxicity

Cancer and cardiovascular disease are the most common causes of mortality in the US, causing approximately 1.2 million deaths annually. The incidence of cancer is expected to increase as the population ages. The prognosis of cancer patients has improved over the last few decades primarily because of newer chemotherapeutic drugs; however, many of these drugs have cardiotoxic side effects. The short-term cardiovascular toxicities of more established drugs are well described; however, understanding of the underlying pathogenesis is increasing. The delayed cardiotoxic effects of cancer treatments have become an important issue contributing to mortality and morbidity as cancer survivorship increases. Chemotherapy-induced cardiotoxicity can manifest in many ways, from asymptomatic decreases in left ventricular ejection fraction to congestive heart failure. Hypertension is commonly seen both as a co-morbidity and a side effect of chemotherapy. In this article, we discuss the pathogenesis, scope, presentation and potential prevention of these toxicities.

Valvular heart disease in patients with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) or “brittle bone disease” is a rare connective tissue hereditary disorder. The most common clinical presentation of OI is bone fractures. OI also involves extraskeletal structures; however, cardiovascular manifestations are rare. In this report, we describe the cardiovascular anomalies of patients with OI who underwent valve surgery and review the literature on this subject. doi: 10.1111/jocs.12064 (J Card Surg 2013;28:139–143)

Intersection of Cardiology and Oncology Clinical Practices

Globally, cancer is diagnosed in approximately 13 million people each year. Approximately 1.6 million cancer patients are seen by cancer clinics across the United States (US) at this time. Over the next two decades, cancer incidence is estimated to increase by approximately 45% to 2.3 million (1). In the US, the 5-year relative survival rate of patients diagnosed with cancer in 1975–1977 was 50%, improving to 68% in the period 1999–2005. Novel targeted chemotherapeutic agents and improved diagnostic techniques are responsible for this increased survival. However, with the improvement in life expectancy, the adverse effects of chemotherapeutic agents, especially cardiotoxicity, is an emerging health problem. Cardiovascular toxicity on its own has a detrimental effect on both the quantity and quality of life independent of the oncological prognosis. Currently, more than two million women with breast cancer are at risk of anthracycline cardiotoxicity in the US (2). Human epidermal growth factor receptor II (HER2) positive disease comprises approximately 25% of all breast cancer patients and is associated with more aggressive disease activity and worse prognosis. Trastuzumab, a humanized monoclonal antibody used for patients with HER2 positive breast cancer in conjugation with chemotherapy, can provide longer survival and 20% reduction in risk of death (3). Cardiotoxicity becomes an important health issue because up to 27% of women with breast cancer receiving anthracyclines, cyclophosphamide, and trastuzumab showed cardiac dysfunction (3). Breast cancer mortality is reduced by approximately one-third, but the risk of heart toxicity is five times more likely for women receiving trastuzumab than women receiving standard therapy alone (4). Patients showing signs of cardiotoxicity often require a dose reduction, a change in the schedule dosing or even cessation of treatment with attendant consequences. Many patients with an asymptomatic decrease in left ventricular ejection fraction (LVEF) are receiving neither the American College of Cardiology/American Heart Association Class I-indicated treatments nor cardiovascular specialty consultation (5). Concern for cardiotoxicity is not restricted to breast cancer survivors. Based on National Cancer Institute (NCI) data, the number of new renal cancer patients in 2013 is expected to be 65,000. In Europe, the incidence of renal cell carcinoma (RCC) has doubled in the last three decades (6). Improved treatment strategies have increased the 5-year survival of patients with RCC from 50% in 1975–1977 to 72% in 2002–2008. Within the last decade, the US Food and Drug Administration (FDA) has approved six drugs for the treatment of RCC including multitargeted tyrosine kinase inhibitors (TKIs); antibodies to vascular endothelial growth factor (VEGF); and mammalian target of rapamycin (mTOR) inhibitors. Sunitinib, a novel multitargeted TKI, has proven efficacy in advanced metastatic RCC demonstrating an increased median progression free survival of 8.3 months in these patients (7). In a study by Hall et al. (8), five of the approved targeted therapy drugs (sorafenib, pazopanib, bevacizumab, everolimus, and temsirolimus) have cardiotoxic side effects. In this 159-patient study, 73% of patients experienced some form of cardiotoxicity ranging from hypertension to severe heart failure (8). In a cohort of patients with renal and non-renal carcinoma, sunitinib was found to be associated with a 3.3-fold higher risk of heart failure (9). Other targeted agents such as imatinib mesylate, Dasatinib, Nilotinib, and Sorafenib are prescribed for treatment of various hematological malignancies, hepatocellular carcinoma (HCC), gastrointestinal stromal tumor (GIST), and myeloproliferative/myelodysplastic diseases and have been shown to be strongly associated to cardiotoxicity (10–13). Imatinib has been shown to be associated with decline in LVEF, especially in patients with other comorbidities including coronary artery disease, diabetes, and hypertension (10).

Cangrelor versus clopidogrel in percutaneous coronary intervention: a systematic review and meta-analysis

AIMS Cangrelor is a new antiplatelet agent that has been used in percutaneous coronary intervention (PCI) with mixed results. We aimed to review the evidence on the efficacy of cangrelor in comparison to clopidogrel in reducing ischaemic endpoints at 48 hours in patients undergoing PCI in large randomised trials. METHODS AND RESULTS In three large clinical trials involving 25,107 participants, the risk of the primary composite efficacy endpoint of death, MI and ischaemia-driven revascularisation at 48 hours, (pooled OR 0.94; 95% CI: 0.77-1.14, p=0.51, I2=68%), death from all cause (pooled OR 0.72, 95% CI: 0.36-1.43, p=0.34, I2=52%), myocardial infarction (pooled OR 0.94, 95% CI: 0.77-1.14, p=0.51, I2=68%) was not significantly different between cangrelor and clopidogrel. Likewise, severe or life-threatening bleeding was similar between cangrelor and clopidogrel (pooled OR 1.21, 95% CI: 0.70-2.12, p=0.50, I2=0%). The risk of stent thrombosis (pooled OR 0.59, 95% CI: 0.43-0.81, p=0.001, I2=0%), Q-wave myocardial infarction (pooled OR 0.53, 95% CI: 0.30-0.92, p=0.02, I2=0%) and ischaemia-driven revascularisation (pooled OR 0.71, 95% CI: 0.52-0.98, p=0.04, I2=0%) was lower in the cangrelor group. CONCLUSIONS Based on this meta-analysis, we did not find any difference in the risk of the primary composite efficacy endpoint of all-cause death, ischaemia-driven revascularisation, and myocardial infarction at 48hours between cangrelor and clopidogrel use. Given that cangrelor was associated with a lower risk of stent thrombosis, ischaemia-driven revascularisation and Q-wave myocardial infarction compared to clopidogrel, cangrelor can be considered as a suitable alternative during PCI.

Anterolateral papillary muscle rupture: An unusual complication of septic coronary embolism

In most cases, acute mitral valve regurgitation in the setting of infective endocarditis is caused by the destruction of either the mitral valve leaflets or the chordal apparatus. A 54-year-old woman had development of respiratory failure due to pulmonary oedema from severe acute mitral valve regurgitation in the setting of acute bacterial endocarditis. She was found to have a ruptured anterolateral papillary muscle from occlusion of the circumflex artery by embolic vegetations arising from the aortic valve. Although this occurrence is uncommon, an embolic phenomenon resulting in myocardial infarction and subsequent rupture of papillary muscle must be considered as a cause of acute severe mitral valve regurgitation.

Occurrence of left-sided heart valve involvement before right-sided heart valve involvement in carcinoid heart disease

Carcinoids are rare neuroendocrine tumours that occur primarily in the gastrointestinal tract. Carcinoid heart disease is characterized by fibrous plaque deposition on the endocardial surface of the cardiac valves and chambers. It affects the right heart valves in 85% of cases and the left heart valves in 15%. We present an unusual case of a patient with metastatic carcinoid heart disease in whom typical carcinoid aortic and mitral valve lesions developed 2 years prior to the development of severe right-sided carcinoid valvular heart disease.