Does the ISCHEMIA Trial Apply to My Patients?

PURPOSE OF REVIEW: The ISCHEMIA trial demonstrated no difference in myocardial infarction or death in patients with stable coronary disease and moderate or large ischemia territory treated either with invasive revascularization or optimal medical therapy. Whether the findings of the randomized control trial relates to real-world outcomes is uncertain. RECENT FINDINGS: Contemporary guideline-directed medical therapy has had a significant impact on the prognosis of coronary artery disease. Various observational data appear to indicate limited generalizability of the ISCHEMIA trial in different populations. Further studies are warranted to evaluate the optimal modality of therapy in patients with stable coronary disease and moderate or severe ischemia. The applicability of ISCHEMIA and ISCHEMIA-CKD trials still requires further validation.

Granular Cell Tumor - An Important Entity to Consider on Upper Gastrointestinal Endoscopy.

Granular cell tumors (GCT) are benign, submucosal tumors derived from neural or Schwann cells. They are commonly found in the oral cavity, skin, breast and tongue. Less commonly, they can also occur in the gastrointestinal tract, usually in the esophagus. We describe two cases of esophageal GCT which were discovered by upper endoscopy (EGD). Case one underwent endoscopic ultrasound (EUS) guided fine needle aspiration and biopsy and case two underwent biopsy of a submucosal nodule. Both biopsies were histologically diagnosed as GCT with supportive S100 positive immunostaining. GCTs are an important diagnosis for physicians to consider in their differential of esophageal nodule or lesion. Though benign, they may rarely show malignant transformation. Therefore, it is essential to have surveillance with EGD/EUS every two to three years if they are not surgically resected.

Mycotic Aneurysm of the Middle Cerebral Artery Leading to Subarachnoid Hemorrhage, as the Initial Presentation of Bartonella henselae Endocarditis.

Bartonella species was first reported as a cause of endocarditis in 1993, currently it is thought to account for 3-4 percent of all diagnosed cases. Initial symptoms of Bartonella endocarditis are non-specific like weight loss, fever and fatigue. There are very few reported cases of Bartonella endocarditis causing mycotic aneurysm. We present a case of a 60-year-old male who presented with subarachnoid hemorrhage secondary to mycotic aneurysm. Due to high suspicion of endocarditis leading to mycotic aneurysm he underwent transesophageal echocardiography which showed mitral valve vegetations. His blood cultures were negative, he was eventually diagnosed with Bartonella henselae by elevated IgG titers greater than 1:800. Due to repeated mycotic aneurysms on antibiotics, he underwent surgical mitral valve replacement along with the full course of antibiotics and has been asymptomatic since.

Right Ventricular Thrombus-in-Transit in Submassive Pulmonary Embolism.

Right heart thrombus (RHT) occurs secondary to deep venous thrombus in transit to pulmonary veins, intra cardiac devices and prosthetic valves. When RHT is present in a patient with pulmonary embolism (PE) it is generally shown to be associated with worse outcomes. Even though multiple trials have studied treatment of PE, the optimal treatment of PE associated with RHT is still largely based on clinical judgment. We present a 73-year- old female patient with submassive PE and right ventricular thrombus in transit, who was successfully treated with ultrasound guided catheter based thrombolysis.

Aspirin in Primary and Secondary Prevention of Cardiovascular Disease.

Aspirin is one of the most widely used drugs for the treatment of cardiovascular disease. While its use in patients with known cardiovascular disease has been supported with trials which have included mortality benefit, the utility of aspirin therapy in patients without established cardiovascular disease has been less clear. Early trials appeared to demonstrate benefit with the use of aspirin, but trials after 2000 did not consistently substantiate using aspirin for primary prevention of cardiovascular disease. Despite the lack of robust supportive evidence, aspirin was recommended and used extensively for primary prevention in patients at higher risk for cardiovascular events. More recently in 2018, results of three randomized, controlled trials: ARRIVE, ASCEND, ASPREE demonstrated modest to no benefit in preventing cardiovascular events and mortality with aspirin use for primary prevention. These trials also demonstrated an increased risk of bleeding in these patients who were on aspirin for primary prevention.

Optical Coherence Tomography in Intracoronary Diagnostics.

Optical coherence tomography (OCT) has been revolutionary in the field of medical imaging since its inception in 1991, especially in the field of ophthalmology, but its use in coronary artery disease (CAD) and percutaneous coronary intervention (PCI) is still to be explored to its full potential. OCT has proven benefits in guiding PCI when it comes to assessing baseline lesion characteristics, plaque burden and its composition. OCT images provide high axial resolution (10 micrometer) in assessing intra and transluminal coronary structures, which is useful in identifying vulnerable thin fibrous cap atheroma (TCFA) and to differentiate plaque rupture from plaque erosion causing acute coronary syndrome. Optimal stent placement and periprocedural complications (for example stent malposition, coronary dissections, thrombosis) can be assessed by OCT post intervention. It has also seen increasing use in studies trying to elucidate evolution of atherosclerosis, effects of therapeutic interventions on coronary artery plaques and to follow long-term stent outcomes. In this review, we focus on an overview of OCT imaging, techniques employed in its use, its clinical and research applications, indications and limitations.

Recurrent Catecholamine-Induced Cardiomyopathy and Hypertensive Emergencies: A presentation of Pheochromocytoma and Related Concerns.

Catecholamine-induced cardiomyopathy (CIC) and pheochromocytoma are both rare entities, and their exact incidence and prevalence are unknown. Pheochromocytoma has been implicated as one of the causes of CIC or Takotsubo syndrome (TTS) by means of case reports and retrospective reviews. However, the evaluation of any patient with TTS and pheochromocytoma is often faced with multiple challenges due to its rarity and atypical presentations, which subsequently leads to delay in diagnosis. Here, we present a case of a 51-year old female who had three distinct episodes of TTS and now presented in a hypertensive emergency with angina, palpitations, headache, nausea, and vomiting. She was treated for non-ST elevation myocardial infarction (NSTEMI) but coronary angiogram revealed patent coronary arteries. Due to the paroxysmal nature of her hypertensive emergencies and variable blood pressure response, pheochromocytoma was suspected. On further evaluation, she was found to have elevated metanephrines and a 6.3 cm left adrenal mass on CT scan. This case emphasizes the importance of considering or identifying pheochromocytoma as an underlying primary etiology for recurrent episodes of TTS and related concerns such as choice of anti-hypertensive agents.

Peristomal variceal hemorrhage at the ileal conduit site due to extrahepatic portosystemic shunt.

Peristomal variceal bleeding is a rare but known complication with portal hypertension. In patients with recurrent peristomal hemorrhage, atypical varices should be considered, and liver cirrhosis should be excluded even with normal liver function tests. We report a case of a 76-year-old male who presented with recurrent ileal conduit site peristomal hemorrhage without known chronic liver disease. His liver function tests were normal, but computed tomography of the abdomen and pelvis showed liver nodularity and peristomal varices. He was diagnosed to have cirrhosis with portal hypertension and further tested positive for active hepatitis C infection. The patient's extrahepatic portosystemic ileal conduit site shunt was successfully treated with transjugular intrahepatic portosystemic shunt and endovascular variceal coiling. This case identifies a situation where it is imperative to identify occult liver cirrhosis with portosystemic shunt as a cause of ileal conduit site recurrent stomal bleeding.

When Absence Seizures Are Not Seizure: A Case of Insulinoma.

Insulinomas are rare neuroendocrine tumors that produce excessive insulin and result in hypoglycemia. It can have a wide spectrum of symptoms and presentations which makes it difficult to diagnose at times. Here we present a 39-year-old woman who presented with intermittent diplopia, confusion, and staring episodes for one month. She had previously been seen by a neurologist who diagnosed her with possible absence seizures. However, evaluation showed that that patient had severe hypoglycaemia even with dextrose infusions. She was diagnosed with insulinoma based on lab work and a biopsy of a pancreatic tail mass. She underwent partial pancreatectomy, and has had a good outcome, with no recurrence of her symptoms. This case highlights the variable presentation of insulinomas, and the challenges faced with its diagnosis.

Spectrum of Ischemic Heart Disease Throughout a Woman's Life Cycle.

Ischemic heart disease (IHD) is the leading cause of morbidity and mortality in both genders; however, young women fare the worst, likely reflecting the more complex spectrum of IHD in women when compared to men. Substantial sex-based differences exist in the underlying risk factors, risk enhancers, presentation, diagnosis, and pathophysiology of IHD that are mainly attributed to the influence of female sex hormones. This article reviews the spectrum of IHD including obstructive epicardial coronary artery disease (CAD), myocardial infarction with no obstructive coronary artery disease, ischemia with no obstructive coronary artery disease, spontaneous coronary artery dissection, coronary microvascular dysfunction, vasospastic angina, and coronary thrombosis/embolism that occur in women throughout various stages of their life cycle. We aim to update clinicians on the diagnosis and management of these various types of IHD and highlight where further randomized controlled studies are needed to determine optimal treatment and inform guideline-directed medical therapy.

Spontaneous Coronary Artery Dissection: An Elusive Disease of the Coronaries.

The articles in our Points to Remember column highlight important "need to know" facts about conditions that cardiovascular healthcare professionals may encounter. These may come from any medical specialty, such as nephrology or neurology. The article in this issue is provided by Swaminathan Perinkulam Sathyanarayanan, MD, Department of Internal Medicine, University of South Dakota, and Smitha Narayana Gowda, MD, and Alpesh Shah, MD, Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist.

Overview of Restrictive Cardiomyopathies.

Restrictive cardiomyopathy (RCM) includes a heterogeneous group of diseases that cause increased myocardial stiffness, leading to impaired ventricular relaxation and severe diastolic dysfunction. Given that it is the least common type of cardiomyopathy, it can be a diagnostic challenge due to its varied pathogenesis, clinical presentation, and diagnostic evaluation. In this review, we provide an overview of different etiologies of RCM and examine the diagnostic and treatment approaches for various types.

Safety and Efficacy of Colchicine in Patients With Coronary Artery Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Given current evidence, the use of colchicine for the prevention of adverse cardiovascular events in patients with coronary artery disease (CAD) remains controversial. METHODS: Multiple databases were queried to identify studies comparing the safety and efficacy of colchicine in patients with acute coronary syndrome (ACS) or stable angina. The relative risk (RR) of major adverse cardiovascular events (MACE) and gastrointestinal (GI) adverse events were calculated using a random-effect model. RESULTS: Six clinical trials comprising a total of 5820 patients were identified. The pooled RR of MACE (0.64, 95% confidence interval (CI) 0.36-1.14, p = 0.13), ACS (0.62, 95% CI 0.27-1.41, p = 0.25), cardiac arrest (0.74, 95% CI 0.26-2.14, p = 0.58), stent restenosis (0.71, 95% CI 0.41-1.23, p = 0.22) and mortality (0.95, 95% CI 0.63-1.42, p = 0.79) with colchicine was not significantly different from placebo or control groups. The overall RR of revascularization (0.53, 95% CI 0.34-0.83, p = 0.005) and stroke (0.26, 95% CI 0.11-0.62, p = 0.002) was significantly lower while the net RR of GI adverse events was significantly higher (HR 2.66, 95% CI 1.21-5.87, p = 0.02) in the colchicine group. Propensity matched cohort, sensitivity and subgroup analysis based on adjusted MACE and dosages of colchicine all mirrored the overall results. CONCLUSION: In patients with CAD presenting with an acute coronary syndrome or stable angina, colchicine might offer no significant reduction in MACE and could potentially be harmful due to a significantly higher risk of GI-related adverse events.

Safety and Efficacy of Colchicine in Patients with Stable CAD and ACS: A Systematic Review and Meta-analysis.

BACKGROUND: Evidence from recent trials has shown conflicting results in terms of the utility of colchicine in patients with coronary artery disease (CAD). METHODS: Multiple databases were queried to identify all randomized controlled trials (RCTs) comparing the merits of colchicine in patients with acute coronary syndrome (ACS) or stable CAD. The pooled relative risk ratio (RR) of major adverse cardiovascular events (MACE), its components, and gastrointestinal (GI) adverse events were computed using a random-effect model. RESULTS: Ten RCTs comprising a total of 12,761 patients were identified. At a median follow-up of 12 months, there was a significantly lower risk of MACE [RR 0.66, 95% confidence interval (CI) 0.45-96], ACS (RR 0.66, 95% CI 0.45-0.96), ischemic stroke (RR 0.42, 95% CI 0.22-0.81), and need for revascularization (RR 0.61, 95% CI 0.42-90) in patients receiving colchicine compared with placebo. A subgroup analysis based on the clinical presentation showed that the significantly lower incidence of MACE and stroke were driven by the patients presenting with ACS. The use of colchicine in patients with stable CAD did not reduce the incidence of MACE (RR 0.55, 95% CI 0.28-1.09), ACS (RR 0.52, 95% CI 0.25-1.08), or stroke (RR 0.61, 95% CI 0.33-1.13). There was no significant difference in the relative risk of cardiac arrest, ACS, cardiovascular mortality, and all-cause mortality between the two groups in both ACS and stable CAD populations. The risk of GI adverse events was significantly higher in patients receiving colchicine (RR 2.10, 95% CI 1.12-3.95). CONCLUSION: In patients presenting with ACS, low-dose colchicine might reduce the incidence of MACE, stroke, and the need for revascularization at long follow-up durations. Colchicine might offer no benefits in reducing the risk of ischemic events in patients with stable angina.

Predictors of Permanent Pacemaker Implantation in Patients Undergoing Transcatheter Aortic Valve Replacement - A Systematic Review and Meta-Analysis.

Background As transcatheter aortic valve replacement (TAVR) technology expands to healthy and lower-risk populations, the burden and predictors of procedure-related complications including the need for permanent pacemaker (PPM) implantation needs to be identified. Methods and Results Digital databases were systematically searched to identify studies reporting the incidence of PPM implantation after TAVR. A random- and fixed-effects model was used to calculate unadjusted odds ratios (OR) for all predictors. A total of 78 studies, recruiting 31 261 patients were included in the final analysis. Overall, 6212 patients required a PPM, with a mean of 18.9% PPM per study and net rate ranging from 0.16% to 51%. The pooled estimates on a random-effects model indicated significantly higher odds of post-TAVR PPM implantation for men (OR, 1.16; 95% CI, 1.04-1.28); for patients with baseline mobitz type-1 second-degree atrioventricular block (OR, 3.13; 95% CI, 1.64-5.93), left anterior hemiblock (OR, 1.43; 95% CI, 1.09-1.86), bifascicular block (OR, 2.59; 95% CI, 1.52-4.42), right bundle-branch block (OR, 2.48; 95% CI, 2.17-2.83), and for periprocedural atriorventricular block (OR, 4.17; 95% CI, 2.69-6.46). The mechanically expandable valves had 1.44 (95% CI, 1.18-1.76), while self-expandable valves had 1.93 (95% CI, 1.42-2.63) fold higher odds of PPM requirement compared with self-expandable and balloon-expandable valves, respectively. Conclusions Male sex, baseline atrioventricular conduction delays, intraprocedural atrioventricular block, and use of mechanically expandable and self-expanding prosthesis served as positive predictors of PPM implantation in patients undergoing TAVR.

Prosthetic Valve Endocarditis in Patients Undergoing TAVR Compared to SAVR: A Systematic Review and Meta-Analysis.

BACKGROUND: The risk of prosthetic valve endocarditis (PVE) in patients who underwent transcatheter aortic valve replacement (TAVR) is presumed to be high. METHODS: Electronic databases were searched to identify articles comparing the rate of PVE in post-TAVR and post-surgical aortic valve replacement (SAVR) patients. Pooled adjusted odds ratio (OR) was computed using a random-effects model. RESULTS: A total of 19 studies consisting of 84,288 patients, were identified. There was no significant difference in the odds of PVE between patients undergoing TAVR and SAVR, at 30-day (OR 0.62, 95% confidence interval (CI) 0.20-1.92, p = 0.41), 1-year (OR 0.99 95% CI 0.89-1.11, p = 0.84), 2-year (OR 1.02 95% CI 0.68-1.54, p = 0.92) and 5-year (OR 1.03 95% CI 0.80-1.33, p = 0.81). A subgroup sensitivity analysis also showed no significant inter-group differences in the rate of PVE at all time points, when stratified by the study design (clinical trial vs. observational), type of TAVR valves used (self-expanding bioprosthetic valves vs. balloon expanded bioprosthetic valves) and surgical risk of patients (high vs. intermediate vs. low). There was no heterogeneity (I2 = 0%) in the outcomes of the included studies at 30-day, 1-year and 2-year, while the heterogeneity in studies at 5-year was minimal (I2 = 22%). CONCLUSIONS: In comparison to SAVR, both short and long-term risk of prosthetic valve endocarditis appears to be identical in patients undergoing TAVR. This risk is unaffected by the type of valve, duration of follow-up, study design and surgical risk of the patients.

Early intervention or watchful waiting for asymptomatic severe aortic valve stenosis: a systematic review and meta-analysis.

BACKGROUND: The management of patients with severe but asymptomatic aortic stenosis is challenging. Evidence on early aortic valve replacement (AVR) versus symptom-driven intervention in these patients is unknown. METHODS: Electronic databases were searched, articles comparing early-AVR with conservative management for severe aortic stenosis were identified. Pooled adjusted odds ratio (OR) was computed using a random-effect model to determine all-cause and cardiovascular mortality. RESULTS: A total of eight studies consisting of 2201 patients were identified. Early-AVR was associated with lower all-cause mortality [OR 0.24, 95% confidence interval (CI) 0.13-0.45, P ≤ 0.00001] and cardiovascular mortality (OR 0.21, 95% CI 0.06-0.70, P = 0.01) compared with conservative management. The number needed to treat to prevent 1 all-cause and cardiovascular mortality was 4 and 9, respectively. The odds of all-cause mortality in a selected patient population undergoing surgical AVR (SAVR) (OR 0.16, 95% CI 0.09-0.29, P ≤ 0.00001) and SAVR or transcatheter AVR (TAVR) (OR 0.53, 95% CI 0.35-0.81, P = 0.003) were significantly lower compared with patients who are managed conservatively. A subgroup sensitivity analysis based on severe aortic stenosis (OR 0.24, 95% CI 0.11-0.52, P = 0.0004) versus very severe aortic stenosis (OR 0.20, 95% CI 0.08-0.51, P = 0.0008) also mirrored the findings of overall results. CONCLUSION: Patients with asymptomatic aortic valve stenosis have lower odds of all-cause and cardiovascular mortality when managed with early-AVR compared with conservative management. However, because of significant heterogeneity in the classification of asymptomatic patients, large scale studies are required.