Challenging Case of Transcatheter Mitral Valve-in-Valve-in-Valve Replacement.

BACKGROUND A 39-year-old man with a complex valvular history of recurrent methicillin-resistant Staphylococcus aureus endocarditis with 2 surgical mitral valve replacements (in 2016 and 2017) followed by transcatheter mitral valve replacement (in 2019) presented with orthopnea, paroxysmal nocturnal dyspnea, chest pain, cough, and progressively worsening dyspnea on exertion. CASE REPORT Extensive workup was performed, including transesophageal echocardiogram, which revealed a malfunctioning, severely stenotic bioprosthetic valve. Left and right heart catheterization revealed mild non-obstructive coronary artery disease and severe pulmonary hypertension. Given the patient's complex medical history, he was deemed to be at an elevated risk for repeat sternotomy and repeat valve replacement surgery. Therefore, he underwent a percutaneous transcatheter mitral valve replacement with a 26-mm SAPIEN 3 Edwards valve placed within the previous 29-mm SAPIEN valve. Post-procedural imaging revealed a well-placed valve with an improved mitral valve gradient. CONCLUSIONS This is one of the few rare cases of mitral valve-in-valve via a transcatheter mitral valve replacement approach with successful deployment of a SAPIEN 3 tissue heart valve. The patient experienced significant reversal of heart failure symptoms and improved exertional tolerance following deployment of the valve and was eventually discharged home in a stable condition.

Gender differences in genotypic distribution of endothelin-1 gene and endothelin receptor A gene in pulmonary hypertension associated with rheumatic mitral valve disease.

INTRODUCTION: The female gender is a risk factor for idiopathic pulmonary arterial hypertension. However, it is unknown whether females with rheumatic mitral valve disease are more predisposed to develop pulmonary hypertension compared to males. AIM: We aimed to investigate whether there was a difference in genotypic distribution of endothelin-1 (ET-1) and endothelin receptor A (ETA) genes between female and male patients of pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD). METHODS: We compared prevalence of ET-1 gene (Lys198Asn) and ETA gene (His323His) polymorphisms according to gender in 123 PH-MVD subjects and 123 healthy controls. RESULTS: The presence of mutant Asn/Asn and either mutant Asn/Asn or heterozygous Lys/Asn genotypes of Lys198Asn polymorphism when compared to Lys/Lys in females showed significant association with higher risk (odds ratio [OR] 4.5; p =0.007 and OR 2.39; p =0.02, respectively). The presence of heterozygous C/T and either mutant T/T or heterozygous C/T genotypes of His323His polymorphism when compared to wild C/C genotype in females showed a significant association with higher risk (OR 1.96; p =0.047 and OR 2.26; p =0.01, respectively). No significant difference was seen in genotypic frequencies in males between PH-MVD subjects and controls. Logistic regression analysis showed that mutant genotype Asn/Asn (p =0.007) and heterozygous genotype Lys/Asn of Lys198Asn polymorphism (p =0.018) were independent predictors of development of PH in females. CONCLUSIONS: ET-1 and ETA gene polymorphisms were more prevalent in females than males in PH-MVD signifying that females with rheumatic heart disease may be more susceptible to develop PH.

Endothelin-1 gene and endothelin receptor A gene polymorphisms in severe pulmonary hypertension associated with rheumatic mitral valve disease.

INTRODUCTION: Endothelin-1 (ET-1) gene polymorphisms are implicated in pathogenesis of idiopathic pulmonary arterial hypertension. METHODS: We studied ET-1 (Lys198Asn and 3A/4A) and endothelin receptor A (ETA) gene (His323His) polymorphisms in 123 subjects with pulmonary hypertension associated with rheumatic mitral valve disease (PH-MVD) and 123 healthy controls. RESULTS: The mutant homozygous Asn/Asn genotype in Lys198Asn and T/T genotype in His323His polymorphism was more prevalent in the PH-MVD group. Presence of Asn/Asn genotype was significantly associated with an increased risk (odds ratio 3.9). CONCLUSIONS: ET-1 and ETA gene polymorphisms are prevalent in the PH-MVD group suggesting that they may predispose to the development of PH.

Left atrial function by two-dimensional speckle tracking echocardiography in patients with severe rheumatic mitral stenosis and pulmonary hypertension.

We studied left atrial (LA) function in severe rheumatic mitral stenosis (MS) patients using two-dimensional speckle tracking echocardiography (STE). Eighty patients with isolated severe MS in sinus rhythm and 40 controls underwent comprehensive echocardiography including STE derived LA strain [reservoir strain (LASr), conduit strain (LAScd) and contractile strain (LASct)]. The mean MVA was 0.93 ± 0.21 cm2. The mean values of LASr (14.73 ± 8.59%), LAScd (-7.61 ± 4.47%) and LASct (-7.16 ± 5.15%) in patients were significantly lower (p < 0.001) vs. controls 44.11 ± 10.44%, -32.45 ± 7.63%, -11.85 ± 6.77% respectively and showed decreasing trend with increasing MS severity and higher NYHA class. In conclusion, LA dysfunction is prevalent in severe MS irrespective of NYHA functional class.

Multimarker risk stratification approach and cardiovascular outcomes in patients with stable coronary artery disease undergoing elective percutaneous coronary intervention.

AIMS: We studied the utility of multimarker risk stratification approach to predict cardiovascular outcomes in patients with stable coronary artery disease, undergoing elective percutaneous coronary intervention (PCI). METHODS: We prospectively evaluated 302 consecutive patients with stable coronary artery disease and normal CPK-MB and cardiac troponin T levels, and who underwent elective PCI at our institution. The following cardiac biomarkers were measured before and between 12 and 24h post-procedure: CK-MB, cardiac troponin T, hs-CRP, and NT-ProBNP. Patients were followed up for a minimum of 6 months. RESULTS: Post-PCI, CPK-MB levels were elevated but below myocardial infarction (MI) range in 70 patients (23%), and in the MI range in 6 patients (2%). Troponin T levels were detectable but below the 99th percentile (microleak) in 32 patients (10.6%) and elevated above the 99th percentile (periprocedural MI) in 104 patients (34.4%). At 9 months' follow-up, 1% died, 2% had stable angina, 10.3% had non-fatal MI, and 87.7% remained asymptomatic. There was no significant difference in clinical events among groups stratified by elevation of one biomarker or multiple biomarkers. CONCLUSION: Single or multiple biomarker strategy in patients with normal baseline biomarkers failed to predict major cardiac events after PCI over medium-term follow-up.

Protease-activated receptor-1 antagonists: focus on SCH 530348.

Currently available antiplatelet agents have shown improved short- and long-term clinical outcomes but are associated with increased bleeding risk, and the rates of recurrent ischemic events still remain high. Selective inhibition of protease-activated receptor-1 for thrombin represents a potential novel strategy to reduce ischemic events without increasing the risk of bleeding. Two protease-activated receptor-1 antagonists are currently being evaluated in clinical trials: SCH 530348 and E5555. Results of phase II trials have shown that SCH 530348, when added to standard antiplatelet therapy, was well tolerated and not associated with increased bleeding risk. Two large-scale phase III trials assessing the efficacy of SCH 530348 in addition to the standard of care are currently ongoing. This review provides an outline of the current status of understanding on platelet thrombin-receptor antagonist SCH 530348, focusing on its pharmacologic properties and clinical development.

Isolated spontaneous renal artery dissection: a case report and review.

We report an interesting case of a 65-year-old gentleman who presented with hypertensive emergency and was found to have an isolated spontaneous dissection of the right renal artery. The dissection was stented via endovascular approach and resulted in marked improvement in blood pressure. Spontaneous renal artery dissection is a difficult condition to diagnose and treat, unless suspected early enough during the course of treatment. Endovascular intervention is the treatment of choice, as failure of conservative treatment may have long lasting clinical implications relating to decreased renal perfusion. Surgical intervention can be associated with high rate of complications.

Major adverse cardiac events in patients with hepatitis C infection treated with bare-metal versus drug-eluting stents.

BACKGROUND: There are no data comparing the long-term outcome of bare-metal stents (BMS) vs drug-eluting stents (DES) in patients with hepatitis C virus (HCV) infection. HYPOTHESIS: In patients with HCV infection, the rate of major adverse cardiac events (MACE) would be less, and the mortality rates similar, in patients treated with DES than in patients treated with BMS. METHODS: The incidence of major adverse cardiac events (MACE) during long-term follow-up, including death, myocardial infarction, and target-vessel revascularization, was investigated in HCV-infected patients who also underwent percutaneous coronary intervention with bare-metal or drug-eluting stents. RESULTS: Of 78 patients studied, BMS were placed in 41 patients and DES stents in 37 patients. Stepwise Cox regression analyses were performed to identify significant independent risk factors for MACE. At 42 +/- 11-month follow-up, MACE occurred in 9 of 41 patients (22%) in the BMS group (mean age 63 +/- 11 years, 66% men) vs in 7 of 37 patients (19%) in the DES group (mean age 61 +/- 9 years, 65% men). There was no significant difference in MACE in the BMS group vs the DES group. This persisted even after controlling for length of the stent, complexity of lesion, and other comorbidities. All-cause mortality was not significantly different in the BMS group vs the DES group (7% vs 5%). CONCLUSIONS: At long-term follow-up of HCV-infected patients with stable liver function, the rates of MACE and of all-cause mortality were similar in the BMS and DES groups.

Racial disparities in prescriptions for cardioprotective drugs and cardiac outcomes in Veterans Affairs Hospitals.

Previous reports have suggested that blacks receive life-saving cardioprotective therapies less often than whites, probably because of a lower socioeconomic status, which leads to poor access to physicians. We questioned whether racial disparity existed in the Veterans Affairs Healthcare System. We examined the Veterans' Integrated Service Network (VISN 16) database with regard to the prescription rates for 4 cardiovascular agents-aspirin, beta blockers, statins, and angiotensin-converting enzyme inhibitors. The database, encompassing 474,565 patients (117,071 blacks and 357,494 whites), was analyzed. Cardioprotective drugs were prescribed significantly less often to black patients than compared to white patients (beta blockers 19.7% vs 24.8%, odds ratio [OR] 0.74, 95% confidence interval [CI] 0.72 to 0.75; statins 20.5% vs 30.2%, OR 0.54, 95% CI 0.52 to 0.55; and angiotensin-converting enzyme inhibitors 27.7% vs 30.0%, OR 0.94, 95% CI 0.92 to 0.96; all p <0.0001, after adjustment for all covariates used in the analysis). Nonetheless, the prescription rates for aspirin were greater among the black patients than among the white patients (OR 1.31, 95% CI 1.27 to 1.35, p <0.001) after adjustment. The black patients received coronary artery bypass grafting less often than did the white patients (0.4% vs 1.21%, OR 0.40% to 0.48%, 95% CI 1.34 to 1.42, p <0.001). After adjustment for the use of cardioprotective drugs and coronary artery bypass grafting, black patients still had greater odds of developing angina (OR 1.38, 95% CI 1.34 to 1.42, p <0.001) and acute myocardial infarction (OR 1.11, 95% CI 1.03 to 1.19, p <0.006) than did white patients in the Department of Veterans Affairs Veterans' Integrated Service Network 16 hospitals. In conclusion, the lower prescription rates of cardioprotective drugs and lower rates of coronary artery bypass grafting might be a partial basis for the high rates of cardiac morbidity among black patients.

Major adverse cardiac events in patients with moderate to severe renal insufficiency treated with first-generation drug-eluting stents.

No data are available comparing the long-term outcome of sirolimus-eluting stents (SESs) versus paclitaxel-eluting stents (PESs) in patients with moderate to severe renal insufficiency. The incidence of major adverse cardiac events (MACE), including death, myocardial infarction, and target vessel revascularization, during long-term follow-up were studied in patients with a glomerular filtration rate of <60 ml/min/1.73 m(2), as measured by the Modification of Diet in Renal Disease (MDRD) study equation, who also underwent percutaneous coronary intervention with drug-eluting stents. Of 428 patients studied, PESs were placed in 287 patients and SESs in 141 patients. Stepwise Cox regression analyses were performed to identify significant independent risk factors for MACE. At 47 + or - 19 months of follow-up, MACE had occurred in 49 (17%) of 287 patients in the PES group (mean age 71 + or - 11 years, 55% men) and in 31 (22%) of 141 patients in the SES group (mean age 71 + or - 12 years, 53% men). No significant difference was found in the MACE rate between the PES and SES groups. This persisted even after controlling for stent length, lesion complexity, and other co-morbidities. Also, all-cause mortality was not significantly different between the PES and SES groups (7.1% vs 8.5%, respectively). In conclusion, during long-term follow-up of patients with moderate to severe renal insufficiency, the rates of MACE and all-cause mortality were similar in the PES and SES groups.

Clopidogrel resistance.

Clopidogrel resistance is an emerging clinical scenario, as antiplatelet therapy has become the cornerstone of modern cardiovascular treatment. This leads to an increase in stent thromboses and recurrent ischemic events which add to the health care costs, and increased periprocedural morbidity and mortality. Management of clopidogrel resistance is challenging as there are no standardized guidelines. The arrival of newer antiplatelet drugs and the detection of genetic polymorphisms in susceptible populations may have an impact on the management. Further trials are needed regarding the target population who should be screened for clopidogrel resistance, a standardized diagnostic test to detect clopidogrel resistance, the role of pharmacogenetics, and the need for tailored therapeutic options for a patient with clopidogrel resistance.

Mechanisms underlying pleiotropic effects of statins.

Statins are the most efficacious hypolipidemic drugs available. Numerous meta-analyses of clinical trials have provided unequivocal evidence that statins are effective and safe in preventing cardiovascular morbidity and mortality in patients with and without pre-existing ischemic heart disease. With widespread usage of statins, its actions other than that of lipid-lowering have started to emerge. Although the effects of statins were initially attributed to a reduction in lipid levels, many benefits are now considered to stem from effects other than lipid modulation. In this review, we describe the mechanisms of these pleiotropic effects and the pathways involved in these effects.

Major adverse cardiac events at long-term follow-up in patients treated with single versus multiple stents during single-vessel percutaneous coronary intervention.

BACKGROUND: Although insertion of multiple stents into a single coronary vessel during single-vessel percutaneous coronary intervention (PCI) is common, there are no data on long-term occurrence of major adverse cardiac events (MACE) in patients treated with multiple stents versus a single stent. METHODS: The incidence of MACE (death, myocardial infarction, or target vessel revascularization) during long-term follow-up was investigated in 634 patients who underwent single-vessel PCI. Of the 634 patients, 319 (50%) had a single stent, and 315 (50%) had multiple stents inserted. Stepwise Cox regression analyses were performed to identify significant independent prognostic factors for MACE. RESULTS: At 47-month follow-up, MACE occurred in 61 of 319 patients (19%) who had a single stent versus in 57 of 315 patients (18%) who had multiple stents (P not significant). Significant independent predictors of MACE were use of vein grafts (hazard ratio = 1.94; 95% CI, 1.24-3.03; P = 0.0038) and use of drug-eluting stents (hazard ratio = 0.49; 95% CI, 0.34-0.72; P = 0.0002). CONCLUSIONS: At long-term follow-up of single-vessel PCI, the incidence of MACE was similar in patients with multiple or single stents inserted even after controlling for the length of stents.

Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients.

BACKGROUND: The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors (statins) reduce serum cholesterol level and cardiovascular morbidity and mortality. However, the effect of statins on glucose metabolism is unclear. Some studies have suggested that statins may cause hyperglycemia by increasing calcium concentration in the islet cells leading to decrease in insulin release or by decreasing GLUT 4-mediated peripheral glucose uptake. METHODS: We analyzed the data in 345,417 patients (mean age 61 +/- 15 years, 94% males, 6% diabetic, 20% statin users) from the Veterans Affairs VISN 16 database. We studied change in fasting plasma glucose (FPG) in this population over a mean time of 2 years between the first available measurement and the last measurement form the most recent recorded visit. Data were limited to patients who had 2 FPG measurements. Diagnosis of diabetes had to be present before the first FPG measurement. RESULTS: Among patients without diabetes, FPG increased with statin use from 98 mg/dL to 105 mg/dL, and among nonstatin users, FPG increased from 97 mg/dL to 101 mg/dL (increase in FPG with statin use P < 0.0001). Among patients with diabetes, FPG increased with statin use from 102 mg/dL to 141 mg/dL, and among nonstatin users, FPG increased from 100 mg/dL to 129 mg/dL (increase in FPG with statin use; P < 0.0001). After adjustment for age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors, the change in FPG in nondiabetic statin users was 7 mg/dL (vs 5 mg/dL in nonstatin users, P < 0.0001) and for diabetic statin users it was 39 mg/dL (vs 32 in nonstatin users, P < 0.0001). CONCLUSIONS: Statin use is associated with a rise of FPG in patients with and without diabetes. This relationship between statin use and rise in FPG is independent of age and use of aspirin, beta-blockers, and angiotensin-converting enzyme inhibitors.

Relation of cardiac troponin I levels with in-hospital mortality in patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage.

Troponin I levels were drawn within 24 hours of stroke in 161 of 175 patients (92%) with ischemic stroke, 94 of 107 patients (88%) with intracerebral hemorrhage, and 96 of 96 patients (100%) with subarachnoid hemorrhage. A troponin level >0.4 ng/ml was considered increased. In patients with ischemic stroke, in-hospital mortality occurred in 15 of 23 patients (65%) with increased troponin I compared with 6 of 138 patients (4%) with normal troponin I (p <0.001). In patients with intracerebral hemorrhage, in-hospital mortality occurred in 9 of 14 patients (64%) with increased troponin I compared with 22 of 80 patients (28%) with normal troponin I (p <0.005). In patients with subarachnoid hemorrhage, in-hospital mortality occurred in 8 of 20 patients (40%) with increased troponin I compared with 8 of 76 patients (11%) with normal troponin I (p <0.005). In conclusion, patients with ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage with elevated troponin I levels have increased in-hospital mortality.

Effect of statins on the development of renal dysfunction.

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) decrease serum cholesterol. Dyslipidemia is believed to be associated with the development of renal dysfunction. It was postulated that statins may reduce the development of renal dysfunction. The effect of statin use on the development of renal dysfunction in 197,551 patients (Department of Veterans Affairs, Veterans Integrated Service Network 16 [VISN16] database) was examined. Of these patients, 29.5% (58,332 patients) were statin users and 70.5% (139,219 patients) were not. Development of renal dysfunction was defined as doubling of baseline creatinine or increase in serum creatinine > or =0.5 mg/dl from the first to last measurement with a minimum of 90 days in between. During 3.1 years of follow-up, 3.4% of patients developed renal dysfunction. After adjustment for demographics, diabetes mellitus, smoking, hypertension, and other medications (mainly angiotensin-converting enzyme inhibitors, calcium channel blockers, and aspirin), use of statins decreased the odds of developing renal dysfunction by 13% (odds ratio [OR] 0.87, 95% confidence interval [CI] 0.82 to 0.92, p <0.0001). The beneficial effect of statins appeared to be independent of the decrease in cholesterol. Other variables that affected the development of renal dysfunction were age (OR 1.04, 95% CI 1.03 to 1.04, p <0.0001), diabetes (OR 1.77, 95% CI 1.68 to 1.86, p <0.0001), hypertension (OR 1.11, 95% CI 1.02 to 1.2, p = 0.0153), and smoking (OR 1.12, 95% CI 1.02 to 1.24, p = 0.0244). In conclusion, statin use may retard the development of renal dysfunction. The beneficial effect of statins in preventing the development of renal dysfunction appears to be independent of their lipid-lowering effect.

Percutaneous intervention on the saphenous vein bypass grafts--long-term outcomes.

BACKGROUND/OBJECTIVE: In this era of drug eluting stents (DES), the long-term outcome of percutaneous intervention (PCI) on saphenous venous grafts (SVG) is unknown. The objective of the study was to compare the long-term outcomes of DES versus bare metal stent (BMS) in this population and to determine the predictors of outcomes. METHODS: We reviewed the medical records of all patients who had PCI performed during January 2003 to February 2005 to obtain data cardiac risk factors, medications at discharge, angiographic details and outcomes. RESULTS: One hundred and nine patient had PCI to SVG; of these, 37 patients received DES and the remaining had BMS. Over a mean follow-up of 33 months, the PCI using DES was associated with 30% restenosis, 35% target vessel revascularization (TVR) and major adverse cardiac event (MACE) rate of 46% versus 35% restenosis, 38% TVR and 50% MACE rate with BMS. There was no significant difference in long-term outcome with DES as compared to BMS. CONCLUSION: There was no difference in the long-term outcomes of PCI on SVG irrespective of the type of stent used.