Myocardial blood flow in patients with hypertrophic cardiomyopathy receiving perindopril (CARAPaCE): a pilot study.

AIMS: Coronary microvascular dysfunction (CMD) represents a powerful independent predictor of adverse outcome in hypertrophic cardiomyopathy (HCM). No treatment for CMD exists. The angiotensin-converting enzyme (ACE)-inhibitor perindopril improves myocardial blood flow (MBF) in animal models of cardiac hypertrophy and in hypertensive patients. Whether HCM patients with CMD may benefit is unknown. METHODS: Fourteen HCM patients aged 18-60 years with CMD [MBF post 0.56 mg/kg dipyridamole (Dip) infusion <2.1 ml/min∗g] were included. Presence of left ventricular outflow obstruction, hypertension and coronary artery disease were exclusion criteria. Perindopril was administered after the initial Dip 13N-NH3 PET study at 10 mg for 6 months. After wash-out, a second PET was performed. MBF before and after treatment was compared. RESULTS: No relevant associations were found between baseline MBF values and sex, genetics, history of angina, type of HCM (apical/classic), maximum left ventricular thickness and left ventricular mass. No significant improvement in Dip-MBF was observed with treatment (1.79 ±â€Š0.30 vs.1.76 ±â€Š0.26 ml/min∗g at baseline; P = 0.59). A limited but significant improvement in Dip-MBF was seen only in the subset without evidence of fibrosis at cardiac MRI (n = 4; 28%; 2.03 ±â€Š0.13 vs.1.77 ±â€Š0.26 ml/min∗g at baseline; P = 0.014). The drug was generally well tolerated: only one patient temporarily stopped the drug, because of cough. CONCLUSION: A 6-month perindopril treatment course in HCM patients with CMD was not associated with significant improvement in Dip-MBF. A limited but significant improvement was observed only in the subset of patients without myocardial fibrosis, suggesting potential utility in early disease stages.

Clinical Implications of "Tailored" Antiplatelet Therapy in Patients With Chronic Total Occlusion.

Background Clopidogrel nonresponsiveness is a prognostic marker after percutaneous coronary intervention. Prasugrel and ticagrelor provide a better platelet inhibition and represent the first-line antiplatelet treatment in acute coronary syndrome. We sought to assess the prognostic impact of high platelet reactivity (HPR) and the potential clinical benefit of a "tailored" escalated or changed antiplatelet therapy in patients with chronic total occlusion. Methods and Results From Florence CTO-PCI (chronic total occlusion-percutaneous coronary intervention) registry, platelet function assessed by light transmission aggregometry, was available for 1101 patients. HPR was defined by adenosine diphosphate test ≥70% and optimal platelet reactivity by adenosine diphosphate test <70%. The endpoint of the study was long-term cardiac survival. Patients were stratified according to light transmission aggregometry results: optimal platelet reactivity (82%) and HPR (18%). Means for the adenosine diphosphate test were 44±16% versus 77±6%, respectively. Three-year survival was significantly higher in the optimal platelet reactivity group compared with HPR patients (95.3±0.8% versus 86.2±2.8%; P<0.001). With the availability of new P2Y12 inhibitors, a deeper platelet inhibition (46±17%) and similar survival to the optimal platelet reactivity group were achieved in patients with HPR on clopidogrel therapy after escalation. Conversely, HPR on clopidogrel therapy "not switched" was associated with cardiac mortality (hazard ratio 2.37; P=0.003) after multivariable adjustment. Conclusions HPR on treatment could be a modifiable prognostic marker by new antiaggregants providing a deeper platelet inhibition associated with clinical outcome improvement in complex chronic total occlusion patients. A "tailored" antiplatelet therapy, also driven by the entity of platelet inhibition, could be useful in these high risk setting patients.

Targeted Medical Therapies for Hypertrophic Cardiomyopathy.

PURPOSE OF REVIEW: The management of hypertrophic cardiomyopathy (HCM) has changed considerably over the years, although molecular therapies targeting core mechanisms of the disease are still lacking. This review provides an overview of the contemporary medical approach to patients with HCM, and of promising novel developments hopefully soon to enter the clinical arena. RECENT FINDINGS: Our perception of therapeutic targets for medical therapy in HCM is rapidly evolving. Novel approaches include myocardial metabolic modulation, late sodium current inhibition, and allosteric myosin inhibition, actively pursued to reduce and hopefully prevent the development of severe HCM phenotypes, improve symptom control, and preserve patients from disease-related complications. Clinical management of patients with HCM should be guided by in-depth knowledge of the complex mechanisms at the energetic, metabolic, and electrophysiologic level. Until new experimental therapies become available, tailored management of modifiable disease manifestations should be pursued, including lifestyle counseling and prevention of comorbidities.

Comprehensive Risk Management in Arrhythmogenic Cardiomyopathy Associated With Autosomal Dominant Carvajal Syndrome: Protecting Families.

In a 37-year-old cardiac arrest survivor with autosomal dominant Carvajal syndrome and arrhythmogenic cardiomyopathy, a desmoplakin mutation was identified. Cascade screening identified 2 affected family members and 2 healthy children carrying the mutation. Strategies for primary and secondary risk prevention emphasize the role of genetic testing in rare cardiomyopathies. (Level of Difficulty: Advanced.).

Impact of complete percutaneous revascularization in elderly patients with chronic total occlusion.

OBJECTIVE: The aim of the study was to assess the prognostic impact of successful chronic total occlusion (CTO) percutaneous coronary intervention (PCI) and completeness of revascularization in the elderly. BACKGROUND: Successful CTO-PCI is associated with clinical benefit. Notwithstanding elderly patients are currently underrepresented in CTO-PCI randomized controlled trials and registries. METHODS: From the Florence CTO-PCI registry 1,405 patients underwent CTO-PCI between 2004 and 2015; out of these, 460 consecutive patients were ≥75 years. End point of the study was long-term cardiac survival. The prognostic impact of successful CTO-PCI and complete revascularization on survival was assessed by Kaplan-Meier estimation and by Cox multivariable regression analysis. RESULTS: Patients were stratified according to success (72%) or failure of CTO-PCI. Completeness of revascularization was achieved in 57% of patients. Five-year cardiac survival was significantly higher in the successful CTO-PCI group (84 ± 3% vs. 72 ± 6%; p = .006) and it was further improved if complete coronary revascularization was achieved (90 ± 3% vs. 68 ± 5%; p < .001). At multivariable analysis, increasing age (hazard ratio [HR] 1.08; p = .001), diabetes (HR 1.55; p = .033), chronic kidney disease (HR 1.96, p = .002), left ventricular ejection fraction <0.40 (HR 2.10; p < .001), and completeness of revascularization (HR 0.58; p < .005) resulted independently associated with long-term cardiac survival. CONCLUSIONS: In the elderly successful CTO-PCI is associated with a long-term survival benefit. The results of this study suggest that, even in the elderly, a CTO-PCI attempt should be considered to achieve complete coronary revascularization.

Life-Threatening Acute Pulmonary Thromboembolism Following Severe Carbon Monoxide Poisoning: A Plausible Association.

A 57-year-old man admitted with severe carbon monoxide (CO) poisoning suffered life-threatening pulmonary embolism (PE) after hyperbaric oxygen therapy, in the absence of other risk factors for thromboembolism, and was successfully treated with thrombolysis. CO is a thrombophilic condition predisposing to PE and active surveillance is advisable. (Level of Difficulty: Advanced.).

Parathyroid hormone may be an early predictor of low serum hemoglobin concentration in patients with not advanced stages of chronic kidney disease.

BACKGROUND: Parathyroid hormone (PTH) has been associated with anemia only in dialysis patients with severe hyperparathyroidism. Whether an association between PTH and hemoglobin also exists in patients with chronic kidney disease not on dialysis (CKD-patients) is still unclear. In this study we evaluated the association between PTH and hemoglobin in CKD-patients without severe secondary hyperparathyroidism. METHODS: Hospitalized patients and outpatients (N = 979) were retrospectively evaluated and categorized according to PTH quartile and serum hemoglobin (<12.0, <11.0, <10.0 g/dl). Gender, diabetes, glomerular filtration rate (GFR), hemoglobin, PTH, markers of mineral metabolism, inflammation, iron status and nutrition were variables of adjustment in univariate and multivariate analysis. RESULTS: An inverse association (p = 0.001) was observed between PTH and hemoglobin in patients as a whole, in diabetics, and in patients with GFR ≤60 ml/min. PTH was the single predictor of low hemoglobin in patients as a whole (unstandardized beta -2.12; p = 0.005), in diabetics (unstandardized beta -8.86; p = 0.007) and in patients with GFR ≤60 ml/min (unstandardized beta -2.52; p = 0.006). For each increase of quartile of PTH the risk of having hemoglobin level <10.0 mg/dl was more than doubled [hazard ratio (HR) 2.79, 95% confidence interval (CI) 2.00-3.88; p = 0.001]. The receiver operating characteristic curve showed that PTH ≥122 pg/ml had 67% sensitivity and 75% specificity in predicting hemoglobin level <10.0 g/dl with area under the curve of 0.758 (95% CI 0.73-0.78). CONCLUSIONS: This study shows a significant inverse association between PTH and hemoglobin levels across the whole spectrum of non-dialysis CKD and a doubled risk of having serum hemoglobin <10.0 mg/dl in the absence of severely deranged PTH concentration. These findings may have clinical relevance in ascertaining the cause of unexplained low hemoglobin levels in CKD-patients.

Impact of BMI on cardiovascular events, renal function, and coronary artery calcification.

BACKGROUND/AIMS: High BMI increases the risk of cardiovascular events (CVEs) in the general population. Conflicting results have been reported on the role of BMI on CVEs and on decline of renal function in patients with chronic kidney disease not on dialysis (CKD). This study evaluates the impact of BMI on CVEs, dialysis initiation, and coronary artery calcification (CAC) in CKD patients. METHODS: CKD patients were divided in normal-BMI and high-BMI patients. CVEs, initiation of dialysis, and extent and progression of CAC were assessed. Univariate and multivariable analysis were performed (adjustment variables: age, diabetes, hypertension, gender, CKD stage, serum concentration of hemoglobin, parathyroid hormone, calcium, phosphorus, albumin, C-reactive protein, LDL-cholesterol, total calcium score, 24-hour proteinuria). Patients were followed to the first event (CVE, dialysis) or for 2 years. RESULTS: 471 patients were evaluated. A CVE occurred in 13.5 and 21.3% (p < 0.05) of normal-BMI and high-BMI patients, respectively. High BMI did not increase the risk for CVEs in univariate (HR: 1.86; 95% CI: 0.97-3.54; p = 0.06) or multivariable analysis (HR: 1.36; 95% CI: 0.57-3.14; p = 0.50). High BMI did not increase the risk for initiation of dialysis in univariate (HR: 0.96; 95% CI: 0.58-1.60; p = 0.9) or multivariable analysis (HR: 1.77; 95% CI: 0.82-3.81; p = 0.14). Adding the interaction term (between BMI and glomerular filtration rate) to other variables, the risk of dialysis initiation significantly increased (HR: 3.06; 95% CI: 1.31-7.18; p = 0.01) in high-BMI patients. High BMI was not a predictor of CAC extent or progression. CONCLUSIONS: High BMI was not a predictor of CVEs. High BMI increased the risk for dialysis initiation, but high BMI was not associated to CAC extent and progression. The presence of confounders may underestimate the impact of high BMI on dialysis initiation.