Coronary microvascular dysfunction and cancer therapy-related cardiovascular toxicity.

BACKGROUND: Coronary microvascular dysfunction (CMD) has been implicated as a potential mechanism in the pathophysiology of different clinical presentations, including ischemia and no obstructive coronary artery disease (INOCA), myocardial infarction and nonobstructive coronary arteries (MINOCA), stress cardiomyopathy, heart failure, and myocarditis. There are limited data about the role of CMD in cancer therapy-related cardiovascular toxicities. CASE PRESENTATIONS: Four women with a diagnosis of active cancer receiving treatment who developed subsequent MINOCA or INOCA presented for cardiac catheterization. Upon coronary angiography showing no obstructive coronary arteries, coronary function testing was performed to evaluate for CMD. METHODS: Coronary physiology was assessed measuring non-hyperemic (resting full-cycle ratio [RFR]) and hyperemic (fractional flow reserve [FFR]) indices using a physiologic pressure wire. The wire also measured coronary flow reserve (CFR), index of microcirculatory resistance (IMR), and RFR using thermodilution technology. CMD was confirmed if the CFR was <2.5 and the IMR was >25. RESULTS: Among 4 patients with diagnosis of active cancer presenting with chest pain, there was no evidence of obstructive coronary artery disease, leading to separate diagnoses of INOCA, MINOCA, stress cardiomyopathy, and myocarditis. We found CMD in 2 patients (1 with INOCA and 1 with immune checkpoint inhibitor-related myocarditis). CONCLUSIONS: CMD may play a role in cardiovascular toxicities. Further coronary physiology studies are needed to understand the mechanisms of cancer therapy-related cardiovascular toxicity and CMD, as well as optimal preventive and treatment options.

Acute limb ischemia from embolization of left ventricular pseudoaneurysm thrombus: a rare case report.

Myocardial infarction (MI) can lead to a wide spectrum of mechanical complications. Left ventricular pseudoaneurysm (LVP) is a rare but serious complication of MI. Case presentation: A 69-year-old woman with prior coronary artery bypass grafting and a remote history of inferolateral ST-elevation MI (STEMI) with failure to revascularize the left circumflex artery presented with gangrenous right toes that appeared 2 years after her STEMI. A computed tomography angiogram of the right lower extremity showed arterial occlusion and mild atherosclerotic disease. Echocardiography revealed a pseudoaneurysm with an adherent mural thrombus as the underlying cause of acute limb ischemia. The patient was started on heparin and cardiothoracic surgery was consulted but did not operate as the risk of surgery outweighed the benefit. On hospital day 3, the patient underwent amputation of her gangrenous toes as the tissue was nonviable. The patient remained stable during her hospital stay and was discharged on day 5 on long-term anticoagulation. Clinical discussion: LVPs have a wide spectrum of presentations, from asymptomatic or nonspecific symptoms to thromboembolism with end-organ damage, such as in our case. Therefore, early diagnosis and management are of paramount importance. Our patient's prior coronary artery bypass grafting most likely helped in forming a fibrous pericardium that sealed the pseudoaneurysm and prevented its rupture. Conclusions: STEMI requires close follow-up, especially in cases where revascularization is not achievable, as the risk of mechanical complications and mortality is high. Physicians should have a high suspicion for LVP in patients with prior MI, given its wide spectrum of presentations.

A systematic review and meta-analysis of the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction.

BACKGROUND: Heart failure with preserved ejection fraction is a complex clinical syndrome marked by different phenotypes and related comorbidities. Transthyretin amyloidosis is an underestimated phenotype. We aim to evaluate the prevalence of transthyretin amyloidosis in heart failure with preserved ejection fraction. METHODS: This meta-analysis was conducted according to PRISMA guidelines. A search strategy was designed to utilize PubMed/Medline, EMBASE, and Google scholar to locate studies whose primary objective was to analyze the prevalence of transthyretin amyloidosis in heart failure preserved ejection fraction. RESULTS: Of 271 studies initially identified, 5 studies comprising 670 patients were included in the final analysis. The prevalence of transthyretin amyloidosis was 11%. Patients with transthyretin amyloid cardiomyopathy were more likely to be males (RR 1.38; 95% CI 1.09 to 1.75; P<0.01; I2=37%), and more likely to have low voltage criteria on ECG (RR 2.98; 95% CI 1.03 to 8.58; P=0.04; I2=75%) compared with transthyretin negative group. They also have higher SMD of age (SMD 0.73; 95% CI 0.48 to 0.97; P<0.01; I2=0%), and NT-proBNP (SMD 0.48; 95% CI 0.02 to 0.93; P=0.04; I2=36%) compared with transthyretin negative group. On reported echocardiogram, they have higher SMD of mass index (SMD 0.77; 95% CI 0.27 to 1.27; P<0.01; I2=65%), posterior wall thickness (SMD 0.92; 95% CI 0.62 to 1.21; P<0.01; I2=0%), and septal wall thickness (SMD 1.49; 95% CI 0.65 to 2.32; P<0.01; I2=87%) compared with transthyretin negative group. CONCLUSION: Transthyretin amyloidosis affects 11% of HFpEF patients. Therefore, screening HFpEF patients at risk of cardiac amyloidosis is warranted.

P2Y12 Inhibitors versus Aspirin Monotherapy for Long-term Secondary Prevention of Atherosclerotic Cardiovascular Disease Events: A Systematic Review and Meta-analysis.

Patients with established atherosclerotic cardiovascular disease (ASCVD) need long-term antiplatelet therapy to decrease the risk of future ASCVD events. We searched PubMed, Cochrane Library, and ClinicalTrials.gov (inception through September 2021) for randomized controlled trials (RCTs) evaluating P2Y12 inhibitors vs aspirin for secondary prevention of ASCVD events. Seven RCTs including a total of 56,982 patients were included in this analysis. The median follow-up duration was 22.8 (IQR 12) months. When P2Y12 inhibitors were compared with aspirin as long-term antiplatelet therapy for secondary prevention of ASCVD events, there was a significant decrease in the risk of myocardial infarction [RR: 0.83; 95% CI: 0.72-0.94], and stroke [RR: 0.90; 95% CI: 0.83-0.99]. However, there was no significant difference in all-cause mortality [RR: 1.02; 95% CI: 0.92-1.12], or cardiovascular mortality [RR: 0.95; 95% CI: 0.83-1.08] between P2Y12 inhibitors and aspirin users. Additionally, there was no significant difference in major bleeding events [RR: 0.88; 95% CI: 0.74-1.04], or all bleeding events [RR: 1.09; 95% CI: 0.90-1.33] between P2Y12 inhibitors and aspirin groups. Use of P2Y12 inhibitor monotherapy is associated with lower rates of myocardial infarction and stroke in ASCVD patients without any significant difference in mortality, or bleeding compared to aspirin monotherapy.

Left main coronary artery vasospasm: A case report of misdiagnosed severe coronary artery disease.

Introduction and importance: Left main coronary artery (LMCA) vasospasm is rare and can cause demand-supply mismatch that can mimic coronary artery disease (CAD). This could lead to misdiagnosis and inappropriate referral for surgical intervention. Case presentation: A 55-year-old woman with no cardiac risk factors presented with anginal chest pain. Vital signs were stable and physical exam was unremarkable. Chest x-ray was normal and electrocardiography (ECG) revealed sinus bradycardia with nonspecific ST-segment and T-wave changes in the inferolateral leads present on prior ECGs. Echocardiography revealed a left ventricular ejection fraction of 60-65% without regional wall motion abnormalities and cardiac troponin was within normal limits. Nuclear stress test was unsuccessful due to severe reaction to regadenoson. Subsequent invasive coronary angiography revealed an isolated 70% stenosis of the LMCA. Patient was referred for surgery, however, coronary computed tomography angiography (CCTA) prior to surgery unmasked spasm and prevented unnecessary surgery. Clinical discussion: Coronary spasm is diagnosed clinically based on typical symptoms, transient ECG changes, and a negative stress test with no regional wall motion abnormalities on echocardiography. During episodes of spasm, coronary angiography would reveal an area of stenosis in the affected coronary segment. This could lead to a misdiagnosis of CAD and, in cases of LMCA stenosis, inappropriate referral for surgical intervention. Conclusion: LMCA spasm is rare but can mimic CAD leading to misdiagnosis and unnecessary surgery. Physicians should have a high suspicion for spasm especially in patients with anginal chest pain who lack CAD risk factors. CCTA can unmask spasm and prevent unnecessary interventions.

Ischemic and Bleeding Outcomes of Potent P2Y12 Inhibitor Antiplatelet Agents Versus Clopidogrel in Elderly Patients With Acute Coronary Syndrome: A Meta-Analysis of Randomized Trials.

BACKGROUND: The role of P2Y12 inhibition in acute coronary syndrome (ACS) has been well described in literature. However, the agent of choice is less clear among elderly patients (>65 years) who are at increased risk of bleeding. This meta-analysis was designed to investigate the efficacy and safety of potent P2Y12 inhibitors vs. clopidogrel in this population. METHODS AND RESULTS: PubMed, Cochrane Central Register of Clinical Trials, EMBASE, and ClinicalTrial.gov (inception through February 25, 2021) were searched for randomized studies comparing potent oral P2Y12 inhibitors to clopidogrel in elderly population presenting with ACS. Study endpoints included major adverse cardiac events (MACE), major bleeding, all-cause mortality, cardiovascular mortality, myocardial infarction, and stroke. Hazard ratios (HRs) with 95% confidence intervals (CIs) were computed and p<0.05 was considered significant. Eight randomized studies with a total 10,081 patients were included in the final analysis. At mean follow up of 26 months, there were no significant differences between potent oral P2Y12 inhibitors and clopidogrel in MACE (HR 0.97, 95% CI [0.82-1.15]; p=0.73), all-cause mortality (HR 0.91, 95% CI [0.75-1.10]; p=1.00), MI (HR 0.95, 95% CI [0.78-1.17]; p=0.64), and stroke (HR 1.24, 95% CI [0.82-1.86]; p=0.31). However, potent oral P2Y12 inhibitors were associated with a reduction in cardiovascular mortality (HR 0.82, 95% CI [0.68-0.98]; p=0.03), and an increase in major bleeding events (HR 1.32, 95% CI [1.09-1.59]; p<0.01). CONCLUSION: In comparison with clopidogrel, the use of potent oral P2Y12 inhibitors in elderly patients with ACS, is associated with a reduction in the risk of cardiovascular mortality with increased risk of bleeding events and no significant change in MACE outcomes.

Valve-in-valve transcatheter aortic valve replacement versus redo surgical valve replacement for degenerated bioprosthetic aortic valve: An updated meta-analysis comparing midterm outcomes.

BACKGROUND: Redo surgical aortic valve replacement (redo SAVR) and valve-in-valve transcatheter aortic valve replacement (ViV TAVR) are the two treatment strategies available for patients with severe symptomatic bioprosthetic aortic valve dysfunction. Herein, we performed a systematic review and meta-analysis comparing both early and mid-term outcomes of ViV TAVR versus redo SAVR in patients with bioprosthetic aortic valve disease. METHODS: PubMed, Cochrane reviews, and Google scholar electronic databases were searched and studies comparing ViV TAVR versus redo SAVR were included. The primary outcome of interest was mid-term (1-5 years) and 1-year all-cause mortality. Secondary outcomes included were 30-day all-cause mortality, myocardial infarction, pacemaker implantation, stroke, acute kidney injury, major or life-threatening bleeding, and postprocedural aortic valve gradients. Pooled risk ratios (RR) with their corresponding 95% confidence intervals (CIs) were calculated for all outcomes using the DerSimonian-Laird random-effects model. RESULTS: Nine observational studies with a total of 2,891 individuals and mean follow-up of 26 months met the inclusion criteria. There is no significant difference in mid-term and 1-year mortality between ViV-TAVR and redo SAVR groups with RR of 1.15 (95% CI 0.99-1.32; p = .06) and 1.06 (95% CI 0.69-1.61; p = .8). 30-day mortality rate was significantly lower in ViV-TAVR group with RR of 0.65 (95% CI 0.45-0.93; p = .02). ViV-TAVR group had lower 30-day bleeding, length of stay, and higher postoperative gradients. CONCLUSION: Our study demonstrates a lower 30-day mortality and similar 1-year and mid-term mortality for ViV TAVR compared to redo SAVR despite a higher baseline risk. Given these findings and the ongoing advances in the transcatheter therapeutics, VIV TAVR should be preferred over redo SAVR particularly in those at intermediate-high surgical risk.

Urinothorax Caused by Xanthogranulomatous Pyelonephritis.

Xanthogranulomatous pyelonephritis is a rare form of chronic pyelonephritis that generally afflicts middle-aged women with a history of recurrent urinary tract infections. Its pathogenesis generally involves calculus obstructive uropathy and its histopathology is characterized by replacement of the renal parenchyma with lipid filled macrophages. This often manifests as an enlarged, nonfunctioning kidney that may be complicated by abscess or fistula. This case details the first reported case of xanthogranulomatous pyelonephritis complicated by urinothorax, which resolved on follow-up chest X-ray after robot-assisted nephrectomy.

Small Cell Carcinoma of Prostate: A Case Report of a Patient With Concomitant Transitional Cell Cancer of the Bladder.

Small cell carcinomas (SCCs) are aggressive neoplasms commonly associated with a pulmonary origin. However, albeit rare, extrapulmonary SCC can occur in a variety of sites with an incidence in North America approximated to be 0.1% to 0.4%. Among these sites, approximately 10% of extrapulmonary SCC cases occur in the prostate and are associated with a poor mortality with a median survival of 10 months. Because of the rarity of the prostatic SCC, there is no formal treatment protocol. In this case report, we present a patient who was diagnosed with SCC in the prostate as primary origin. Adjuvant concurrent chemoradiotherapy was started, which he is tolerating so far. While the management of metastatic disease is well documented with the use of chemotherapy, specific data on nonmetastatic disease is lacking. As some studies suggest, a combined surgical and chemotherapeutic approach is helpful in localized disease. In our case, this approach has led to a good clinical outcome in a disease that does not usually allow such results.